1932

Abstract

Lysosomes are the degradative endpoints of material delivered by endocytosis and autophagy and are therefore particularly prone to damage. Membrane permeabilization or full rupture of lysosomal or late endosomal compartments is highly deleterious because it threatens cellular homeostasis and can elicit cell death and inflammatory signaling. Cells have developed a complex response to endo-lysosomal damage that largely consists of three branches. Initially, a number of repair pathways are activated to restore the integrity of the lysosomal membrane. If repair fails or if damage is too extensive, lysosomes are isolated and degraded by a form of selective autophagy termed lysophagy. Meanwhile, an mTORC1-governed signaling cascade drives biogenesis and regeneration of new lysosomal components to reestablish the full lysosomal capacity of the cell. This damage response is vital to counteract the effects of various conditions, including neurodegeneration and infection, and can constitute a critical vulnerability in cancer cells.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-biochem-030222-102505
2024-08-02
2025-02-08
Loading full text...

Full text loading...

/deliver/fulltext/biochem/93/1/annurev-biochem-030222-102505.html?itemId=/content/journals/10.1146/annurev-biochem-030222-102505&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Ballabio A, Bonifacino JS. 2020.. Lysosomes as dynamic regulators of cell and organismal homeostasis. . Nat. Rev. Mol. Cell Biol. 21::10118
    [Crossref] [Google Scholar]
  2. 2.
    Saftig P, Klumperman J. 2009.. Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function. . Nat. Rev. Mol. Cell Biol. 10::62335
    [Crossref] [Google Scholar]
  3. 3.
    Yim WW, Mizushima N. 2020.. Lysosome biology in autophagy. . Cell Discov. 6::6
    [Crossref] [Google Scholar]
  4. 4.
    Rudnik S, Damme M. 2021.. The lysosomal membrane—export of metabolites and beyond. . FEBS J. 288::416882
    [Crossref] [Google Scholar]
  5. 5.
    Papadopoulos C, Meyer H. 2017.. Detection and clearance of damaged lysosomes by the endo-lysosomal damage response and lysophagy. . Curr. Biol. 27::R133041
    [Crossref] [Google Scholar]
  6. 6.
    Wang F, Gomez-Sintes R, Boya P. 2018.. Lysosomal membrane permeabilization and cell death. . Traffic 19::91831
    [Crossref] [Google Scholar]
  7. 7.
    Goldman R, Kaplan A. 1973.. Rupture of rat liver lysosomes mediated by l-amino acid esters. . Biochim. Biophys. Acta Biomembr. 318::20516
    [Crossref] [Google Scholar]
  8. 8.
    Thiele DL, Lipsky PE. 1990.. Mechanism of l-leucyl-l-leucine methyl ester-mediated killing of cytotoxic lymphocytes: dependence on a lysosomal thiol protease, dipeptidyl peptidase I, that is enriched in these cells. . PNAS 87::8387
    [Crossref] [Google Scholar]
  9. 9.
    Miller DK, Griffiths E, Lenard J, Firestone RA. 1983.. Cell killing by lysosomotropic detergents. . J. Cell Biol. 97::184151
    [Crossref] [Google Scholar]
  10. 10.
    Boya P, Kroemer G. 2008.. Lysosomal membrane permeabilization in cell death. . Oncogene 27::643451
    [Crossref] [Google Scholar]
  11. 11.
    Gabande-Rodriguez E, Perez-Canamas A, Soto-Huelin B, Mitroi DN, Sanchez-Redondo S, et al. 2019.. Lipid-induced lysosomal damage after demyelination corrupts microglia protective function in lysosomal storage disorders. . EMBO J. 38::e99553
    [Crossref] [Google Scholar]
  12. 12.
    Yim WW, Yamamoto H, Mizushima N. 2022.. Annexins A1 and A2 are recruited to larger lysosomal injuries independently of ESCRTs to promote repair. . FEBS Lett. 596::9911003
    [Crossref] [Google Scholar]
  13. 13.
    Hasegawa J, Maejima I, Iwamoto R, Yoshimori T. 2015.. Selective autophagy: lysophagy. . Methods 75::12832
    [Crossref] [Google Scholar]
  14. 14.
    Shi X, Mao Y, Daniel LN, Saffiotti U, Dalal NS, Vallyathan V. 1994.. Silica radical-induced DNA damage and lipid peroxidation. . Environ. Health Perspect. 102:(Suppl. 10):14954
    [Google Scholar]
  15. 15.
    Logan T, Simon MJ, Rana A, Cherf GM, Srivastava A, et al. 2021.. Rescue of a lysosomal storage disorder caused by Grn loss of function with a brain penetrant progranulin biologic. . Cell 184::465168.e25
    [Crossref] [Google Scholar]
  16. 16.
    Tseng WA, Thein T, Kinnunen K, Lashkari K, Gregory MS, et al. 2013.. NLRP3 inflammasome activation in retinal pigment epithelial cells by lysosomal destabilization: implications for age-related macular degeneration. . Invest. Ophthalmol. Vis. Sci. 54::11020
    [Crossref] [Google Scholar]
  17. 17.
    Gomez-Sintes R, Ledesma MD, Boya P. 2016.. Lysosomal cell death mechanisms in aging. . Ageing Res. Rev. 32::15068
    [Crossref] [Google Scholar]
  18. 18.
    Freeman D, Cedillos R, Choyke S, Lukic Z, McGuire K, et al. 2013.. Alpha-synuclein induces lysosomal rupture and cathepsin dependent reactive oxygen species following endocytosis. . PLOS ONE 8::e62143
    [Crossref] [Google Scholar]
  19. 19.
    Ditaranto K, Tekirian TL, Yang AJ. 2001.. Lysosomal membrane damage in soluble Aβ-mediated cell death in Alzheimer's disease. . Neurobiol. Dis. 8::1931
    [Crossref] [Google Scholar]
  20. 20.
    Papadopoulos C, Kirchner P, Bug M, Grum D, Koerver L, et al. 2017.. VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy. . EMBO J. 36::13550
    [Crossref] [Google Scholar]
  21. 21.
    Zhang KR, Jankowski CSR, Marshall R, Nair R, Gomez NM, et al. 2023.. Oxidative stress induces lysosomal membrane permeabilization and ceramide accumulation in retinal pigment epithelial cells. . Dis. Model. Mech. 16:(7):dmm050066
    [Crossref] [Google Scholar]
  22. 22.
    Hung YH, Chen LM, Yang JY, Yang WY. 2013.. Spatiotemporally controlled induction of autophagy-mediated lysosome turnover. . Nat. Commun. 4::2111
    [Crossref] [Google Scholar]
  23. 23.
    Kravic B, Bionda T, Siebert A, Gahlot P, Levantovsky S, et al. 2022.. Ubiquitin profiling of lysophagy identifies actin stabilizer CNN2 as a target of VCP/p97 and uncovers a link to HSPB1. . Mol. Cell 82::263349.e7
    [Crossref] [Google Scholar]
  24. 24.
    Terman A, Kurz T. 2013.. Lysosomal iron, iron chelation, and cell death. . Antioxid. Redox Signal. 18::88898
    [Crossref] [Google Scholar]
  25. 25.
    López-Jiménez AT, Cardenal-Muñoz E, Leuba F, Gerstenmaier L, Barisch C, et al. 2018.. The ESCRT and autophagy machineries cooperate to repair ESX-1-dependent damage at the Mycobacterium-containing vacuole but have opposite impact on containing the infection. . PLOS Pathog. 14::e1007501
    [Crossref] [Google Scholar]
  26. 26.
    Kreibich S, Emmenlauer M, Fredlund J, Ramo P, Munz C, et al. 2015.. Autophagy proteins promote repair of endosomal membranes damaged by the Salmonella type three secretion system 1. . Cell Host Microbe 18::52737
    [Crossref] [Google Scholar]
  27. 27.
    Thurston TL, Wandel MP, von Muhlinen N, Foeglein A, Randow F. 2012.. Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion. . Nature 482::41418
    [Crossref] [Google Scholar]
  28. 28.
    Hornung V, Bauernfeind F, Halle A, Samstad EO, Kono H, et al. 2008.. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. . Nat. Immunol. 9::84756
    [Crossref] [Google Scholar]
  29. 29.
    Kroemer G, Jaattela M. 2005.. Lysosomes and autophagy in cell death control. . Nat. Rev. Cancer 5::88697
    [Crossref] [Google Scholar]
  30. 30.
    Petersen NH, Olsen OD, Groth-Pedersen L, Ellegaard AM, Bilgin M, et al. 2013.. Transformation-associated changes in sphingolipid metabolism sensitize cells to lysosomal cell death induced by inhibitors of acid sphingomyelinase. . Cancer Cell 24::37993
    [Crossref] [Google Scholar]
  31. 31.
    Aman Y, Schmauck-Medina T, Hansen M, Morimoto RI, Simon AK, et al. 2021.. Autophagy in healthy aging and disease. . Nat. Aging 1::63450
    [Crossref] [Google Scholar]
  32. 32.
    Zoncu R, Perera RM. 2022.. Built to last: lysosome remodeling and repair in health and disease. . Trends Cell Biol. 32::597610
    [Crossref] [Google Scholar]
  33. 33.
    Yang H, Tan JX. 2023.. Lysosomal quality control: molecular mechanisms and therapeutic implications. . Trends Cell Biol. 33:(9):74964
    [Crossref] [Google Scholar]
  34. 34.
    Hoyer MJ, Swarup S, Harper JW. 2022.. Mechanisms controlling selective elimination of damaged lysosomes. . Curr. Opin. Physiol. 29::100590
    [Crossref] [Google Scholar]
  35. 35.
    Papadopoulos C, Kravic B, Meyer H. 2020.. Repair or lysophagy: dealing with damaged lysosomes. . J. Mol. Biol. 432::23139
    [Crossref] [Google Scholar]
  36. 36.
    Saftig P, Puertollano R. 2021.. How lysosomes sense, integrate, and cope with stress. . Trends Biochem. Sci. 46::97112
    [Crossref] [Google Scholar]
  37. 37.
    Fujita N, Morita E, Itoh T, Tanaka A, Nakaoka M, et al. 2013.. Recruitment of the autophagic machinery to endosomes during infection is mediated by ubiquitin. . J. Cell Biol. 203::11528
    [Crossref] [Google Scholar]
  38. 38.
    Durgan J, Florey O. 2022.. Many roads lead to CASM: Diverse stimuli of noncanonical autophagy share a unifying molecular mechanism. . Sci. Adv. 8::eabo1274
    [Crossref] [Google Scholar]
  39. 39.
    Goodall EA, Kraus F, Harper JW. 2022.. Mechanisms underlying ubiquitin-driven selective mitochondrial and bacterial autophagy. . Mol. Cell 82::150113
    [Crossref] [Google Scholar]
  40. 40.
    Deretic V. 2021.. Autophagy in inflammation, infection, and immunometabolism. . Immunity 54::43753
    [Crossref] [Google Scholar]
  41. 41.
    Randow F, Youle RJ. 2014.. Self and nonself: how autophagy targets mitochondria and bacteria. . Cell Host Microbe 15::40311
    [Crossref] [Google Scholar]
  42. 42.
    Grumati P, Dikic I. 2018.. Ubiquitin signaling and autophagy. . J. Biol. Chem. 293::540413
    [Crossref] [Google Scholar]
  43. 43.
    Raben N, Takikita S, Pittis MG, Bembi B, Marie SK, et al. 2007.. Deconstructing Pompe disease by analyzing single muscle fibers: “to see a world in a grain of sand…. .” Autophagy 3::54652
    [Crossref] [Google Scholar]
  44. 44.
    Repnik U, Borg Distefano M, Speth MT, Ng MYW, Progida C, et al. 2017.. l-leucyl-l-leucine methyl ester does not release cysteine cathepsins to the cytosol but inactivates them in transiently permeabilized lysosomes. . J. Cell Sci. 130::312440
    [Crossref] [Google Scholar]
  45. 45.
    Maejima I, Takahashi A, Omori H, Kimura T, Takabatake Y, et al. 2013.. Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury. . EMBO J. 32::233647
    [Crossref] [Google Scholar]
  46. 46.
    Shinoda W. 2016.. Permeability across lipid membranes. . Biochim. Biophys. Acta Biomembr. 1858::225465
    [Crossref] [Google Scholar]
  47. 47.
    Gurtovenko AA, Anwar J, Vattulainen I. 2010.. Defect-mediated trafficking across cell membranes: insights from in silico modeling. . Chem. Rev. 110::6077103
    [Crossref] [Google Scholar]
  48. 48.
    Marrink SJ, de Vries AH, Tieleman DP. 2009.. Lipids on the move: simulations of membrane pores, domains, stalks and curves. . Biochim. Biophys. Acta Biomembr. 1788::14968
    [Crossref] [Google Scholar]
  49. 49.
    Frallicciardi J, Melcr J, Siginou P, Marrink SJ, Poolman B. 2022.. Membrane thickness, lipid phase and sterol type are determining factors in the permeability of membranes to small solutes. . Nat. Commun. 13::1605
    [Crossref] [Google Scholar]
  50. 50.
    Paula S, Volkov AG, Van Hoek AN, Haines TH, Deamer DW. 1996.. Permeation of protons, potassium ions, and small polar molecules through phospholipid bilayers as a function of membrane thickness. . Biophys. J. 70::33948
    [Crossref] [Google Scholar]
  51. 51.
    Repnik U, Hafner Cesen M, Turk B. 2014.. Lysosomal membrane permeabilization in cell death: concepts and challenges. . Mitochondrion 19:(Part A):4957
    [Crossref] [Google Scholar]
  52. 52.
    Kagedal K, Zhao M, Svensson I, Brunk UT. 2001.. Sphingosine-induced apoptosis is dependent on lysosomal proteases. . Biochem. J. 359::33543
    [Crossref] [Google Scholar]
  53. 53.
    Heerklotz H. 2008.. Interactions of surfactants with lipid membranes. . Q. Rev. Biophys. 41::20564
    [Crossref] [Google Scholar]
  54. 54.
    Boonnoy P, Jarerattanachat V, Karttunen M, Wong-Ekkabut J. 2015.. Bilayer deformation, pores, and micellation induced by oxidized lipids. . J. Phys. Chem. Lett. 6::488488
    [Crossref] [Google Scholar]
  55. 55.
    Tepper HL, Voth GA. 2005.. Protons may leak through pure lipid bilayers via a concerted mechanism. . Biophys. J. 88::3095108
    [Crossref] [Google Scholar]
  56. 56.
    Van der Paal J, Neyts EC, Verlackt CCW, Bogaerts A. 2016.. Effect of lipid peroxidation on membrane permeability of cancer and normal cells subjected to oxidative stress. . Chem. Sci. 7::48998
    [Crossref] [Google Scholar]
  57. 57.
    Wiczew D, Szulc N, Tarek M. 2021.. Molecular dynamics simulations of the effects of lipid oxidation on the permeability of cell membranes. . Bioelectrochemistry 141::107869
    [Crossref] [Google Scholar]
  58. 58.
    de Duve C, de Barsy T, Poole B, Trouet A, Tulkens P, Van Hoof F. 1974.. Lysosomotropic agents. . Biochem. Pharmacol. 23::2495531
    [Crossref] [Google Scholar]
  59. 59.
    Cooper ST, McNeil PL. 2015.. Membrane repair: mechanisms and pathophysiology. . Physiol. Rev. 95::120540
    [Crossref] [Google Scholar]
  60. 60.
    Zhen Y, Radulovic M, Vietri M, Stenmark H. 2021.. Sealing holes in cellular membranes. . EMBO J. 40::e106922
    [Crossref] [Google Scholar]
  61. 61.
    Bour A, Kruglik SG, Chabanon M, Rangamani P, Puff N, Bonneau S. 2019.. Lipid unsaturation properties govern the sensitivity of membranes to photoinduced oxidative stress. . Biophys. J. 116::91020
    [Crossref] [Google Scholar]
  62. 62.
    Sankhagowit S, Wu SH, Biswas R, Riche CT, Povinelli ML, Malmstadt N. 2014.. The dynamics of giant unilamellar vesicle oxidation probed by morphological transitions. . Biochim. Biophys. Acta Biomembr. 1838::261524
    [Crossref] [Google Scholar]
  63. 63.
    Wong-Ekkabut J, Xu Z, Triampo W, Tang IM, Tieleman DP, Monticelli L. 2007.. Effect of lipid peroxidation on the properties of lipid bilayers: a molecular dynamics study. . Biophys. J. 93::422536
    [Crossref] [Google Scholar]
  64. 64.
    Ulmschneider MB, Smith JC, Ulmschneider JP. 2010.. Peptide partitioning properties from direct insertion studies. . Biophys. J. 98::L6062
    [Crossref] [Google Scholar]
  65. 65.
    Stark M, Silva TFD, Levin G, Machuqueiro M, Assaraf YG. 2020.. The lysosomotropic activity of hydrophobic weak base drugs is mediated via their intercalation into the lysosomal membrane. . Cells 9::1082
    [Crossref] [Google Scholar]
  66. 66.
    Skowyra ML, Schlesinger PH, Naismith TV, Hanson PI. 2018.. Triggered recruitment of ESCRT machinery promotes endolysosomal repair. . Science 360::eaar5078
    [Crossref] [Google Scholar]
  67. 67.
    Zhang X, Cheng X, Yu L, Yang J, Calvo R, et al. 2016.. MCOLN1 is a ROS sensor in lysosomes that regulates autophagy. . Nat. Commun. 7::12109
    [Crossref] [Google Scholar]
  68. 68.
    Hu M, Zhou N, Cai W, Xu H. 2022.. Lysosomal solute and water transport. . J. Cell Biol. 221::e202109133
    [Crossref] [Google Scholar]
  69. 69.
    Schmiege P, Fine M, Blobel G, Li X. 2017.. Human TRPML1 channel structures in open and closed conformations. . Nature 550::36670
    [Crossref] [Google Scholar]
  70. 70.
    Miao Y, Li G, Zhang X, Xu H, Abraham SN. 2015.. A TRP channel senses lysosome neutralization by pathogens to trigger their expulsion. . Cell 161::130619
    [Crossref] [Google Scholar]
  71. 71.
    Ellison CJ, Kukulski W, Boyle KB, Munro S, Randow F. 2020.. Transbilayer movement of sphingomyelin precedes catastrophic breakage of enterobacteria-containing vacuoles. . Curr. Biol. 30::297483.e6
    [Crossref] [Google Scholar]
  72. 72.
    Niekamp P, Scharte F, Sokoya T, Vittadello L, Kim Y, et al. 2022.. Ca2+-activated sphingomyelin scrambling and turnover mediate ESCRT-independent lysosomal repair. . Nat. Commun. 13::1875
    [Crossref] [Google Scholar]
  73. 73.
    Boyle KB, Ellison CJ, Elliott PR, Schuschnig M, Grimes K, et al. 2023.. TECPR1 conjugates LC3 to damaged endomembranes upon detection of sphingomyelin exposure. . EMBO J. 42::e113012
    [Crossref] [Google Scholar]
  74. 74.
    Corkery DP, Castro-Gonzalez S, Knyazeva A, Herzog LK, Wu YW. 2023.. An ATG12-ATG5-TECPR1 E3-like complex regulates unconventional LC3 lipidation at damaged lysosomes. . EMBO Rep. 24::e56841
    [Crossref] [Google Scholar]
  75. 75.
    Kaur N, de la Ballina LR, Haukaas HS, Torgersen ML, Radulovic M, et al. 2023.. TECPR1 is activated by damage-induced sphingomyelin exposure to mediate noncanonical autophagy. . EMBO J. 42::e113105
    [Crossref] [Google Scholar]
  76. 76.
    Antonny B. 2011.. Mechanisms of membrane curvature sensing. . Annu. Rev. Biochem. 80::10123
    [Crossref] [Google Scholar]
  77. 77.
    Johannes L, Jacob R, Leffler H. 2018.. Galectins at a glance. . J. Cell Sci. 131::jcs208884
    [Crossref] [Google Scholar]
  78. 78.
    Chauhan S, Kumar S, Jain A, Ponpuak M, Mudd MH, et al. 2016.. TRIMs and galectins globally cooperate and TRIM16 and Galectin-3 co-direct autophagy in endomembrane damage homeostasis. . Dev. Cell 39::1327
    [Crossref] [Google Scholar]
  79. 79.
    Aits S, Kricker J, Liu B, Ellegaard AM, Hamalisto S, et al. 2015.. Sensitive detection of lysosomal membrane permeabilization by lysosomal galectin puncta assay. . Autophagy 11::140824
    [Crossref] [Google Scholar]
  80. 80.
    Eapen VV, Swarup S, Hoyer MJ, Paulo JA, Harper W. 2021.. Quantitative proteomics reveals the selectivity of ubiquitin-binding autophagy receptors in the turnover of damaged lysosomes by lysophagy. . eLife 10::e72328
    [Crossref] [Google Scholar]
  81. 81.
    Radulovic M, Schink KO, Wenzel EM, Nahse V, Bongiovanni A, et al. 2018.. ESCRT-mediated lysosome repair precedes lysophagy and promotes cell survival. . EMBO J. 37::e99753
    [Crossref] [Google Scholar]
  82. 82.
    Vietri M, Radulovic M, Stenmark H. 2020.. The many functions of ESCRTs. . Nat. Rev. Mol. Cell Biol. 21::2542
    [Crossref] [Google Scholar]
  83. 83.
    Shukla S, Larsen KP, Ou C, Rose K, Hurley JH. 2022.. In vitro reconstitution of calcium-dependent recruitment of the human ESCRT machinery in lysosomal membrane repair. . PNAS 119::e2205590119
    [Crossref] [Google Scholar]
  84. 84.
    Herbst S, Campbell P, Harvey J, Bernard EM, Papayannopoulos V, et al. 2020.. LRRK2 activation controls the repair of damaged endomembranes in macrophages. . EMBO J. 39::e104494
    [Crossref] [Google Scholar]
  85. 85.
    Henne WM, Buchkovich NJ, Emr SD. 2011.. The ESCRT pathway. . Dev. Cell 21::7791
    [Crossref] [Google Scholar]
  86. 86.
    Zhu L, Jorgensen JR, Li M, Chuang YS, Emr SD. 2017.. ESCRTs function directly on the lysosome membrane to downregulate ubiquitinated lysosomal membrane proteins. . eLife 6::e26403
    [Crossref] [Google Scholar]
  87. 87.
    Zhang W, Yang X, Chen L, Liu YY, Venkatarangan V, et al. 2021.. A conserved ubiquitin- and ESCRT-dependent pathway internalizes human lysosomal membrane proteins for degradation. . PLOS Biol. 19::e3001361
    [Crossref] [Google Scholar]
  88. 88.
    Sakamaki JI, Ode KL, Kurikawa Y, Ueda HR, Yamamoto H, Mizushima N. 2022.. Ubiquitination of phosphatidylethanolamine in organellar membranes. . Mol. Cell 82::367792.e11
    [Crossref] [Google Scholar]
  89. 89.
    Lee C, Lamech L, Johns E, Overholtzer M. 2020.. Selective lysosome membrane turnover is induced by nutrient starvation. . Dev. Cell 55::28997.e4
    [Crossref] [Google Scholar]
  90. 90.
    Tan JX, Finkel T. 2022.. A phosphoinositide signalling pathway mediates rapid lysosomal repair. . Nature 609::81521
    [Crossref] [Google Scholar]
  91. 91.
    Radulovic M, Wenzel EM, Gilani S, Holland LK, Lystad AH, et al. 2022.. Cholesterol transfer via endoplasmic reticulum contacts mediates lysosome damage repair. . EMBO J. 41::e112677
    [Crossref] [Google Scholar]
  92. 92.
    Wong LH, Gatta AT, Levine TP. 2019.. Lipid transfer proteins: the lipid commute via shuttles, bridges and tubes. . Nat. Rev. Mol. Cell Biol. 20::85101
    [Crossref] [Google Scholar]
  93. 93.
    de la Ballina LR, Munson MJ, Simonsen A. 2020.. Lipids and lipid-binding proteins in selective autophagy. . J. Mol. Biol. 432::13559
    [Crossref] [Google Scholar]
  94. 94.
    Gupta S, Yano J, Mercier V, Htwe HH, Shin HR, et al. 2021.. Lysosomal retargeting of Myoferlin mitigates membrane stress to enable pancreatic cancer growth. . Nat. Cell Biol. 23::23242
    [Crossref] [Google Scholar]
  95. 95.
    Vargas JNS, Hamasaki M, Kawabata T, Youle RJ, Yoshimori T. 2023.. The mechanisms and roles of selective autophagy in mammals. . Nat. Rev. Mol. Cell Biol. 24::16785
    [Crossref] [Google Scholar]
  96. 96.
    Yamamoto H, Zhang S, Mizushima N. 2023.. Autophagy genes in biology and disease. . Nat. Rev. Genet. 24::382400
    [Crossref] [Google Scholar]
  97. 97.
    Levine B, Kroemer G. 2019.. Biological functions of autophagy genes: a disease perspective. . Cell 176::1142
    [Crossref] [Google Scholar]
  98. 98.
    Vargas JNS, Wang C, Bunker E, Hao L, Maric D, et al. 2019.. Spatiotemporal control of ULK1 activation by NDP52 and TBK1 during selective autophagy. . Mol. Cell 74::34762.e6
    [Crossref] [Google Scholar]
  99. 99.
    Ravenhill BJ, Boyle KB, von Muhlinen N, Ellison CJ, Masson GR, et al. 2019.. The cargo receptor NDP52 initiates selective autophagy by recruiting the ULK complex to cytosol-invading bacteria. . Mol. Cell 74::32029.e6
    [Crossref] [Google Scholar]
  100. 100.
    Shi X, Chang C, Yokom AL, Jensen LE, Hurley JH. 2020.. The autophagy adaptor NDP52 and the FIP200 coiled-coil allosterically activate ULK1 complex membrane recruitment. . eLife 9::e59099
    [Crossref] [Google Scholar]
  101. 101.
    Turco E, Witt M, Abert C, Bock-Bierbaum T, Su MY, et al. 2019.. FIP200 claw domain binding to p62 promotes autophagosome formation at ubiquitin condensates. . Mol. Cell 74::33046.e11
    [Crossref] [Google Scholar]
  102. 102.
    Kirkin V, Rogov VV. 2019.. A diversity of selective autophagy receptors determines the specificity of the autophagy pathway. . Mol. Cell 76::26885
    [Crossref] [Google Scholar]
  103. 103.
    Jia J, Bissa B, Brecht L, Allers L, Choi SW, et al. 2020.. AMPK, a regulator of metabolism and autophagy, is activated by lysosomal damage via a novel galectin-directed ubiquitin signal transduction system. . Mol. Cell 77::95169.e9
    [Crossref] [Google Scholar]
  104. 104.
    Maeda S, Otomo C, Otomo T. 2019.. The autophagic membrane tether ATG2A transfers lipids between membranes. . eLife 8::e45777
    [Crossref] [Google Scholar]
  105. 105.
    Osawa T, Kotani T, Kawaoka T, Hirata E, Suzuki K, et al. 2019.. Atg2 mediates direct lipid transfer between membranes for autophagosome formation. . Nat. Struct. Mol. Biol. 26::28188
    [Crossref] [Google Scholar]
  106. 106.
    Valverde DP, Yu S, Boggavarapu V, Kumar N, Lees JA, et al. 2019.. ATG2 transports lipids to promote autophagosome biogenesis. . J. Cell Biol. 218::178798
    [Crossref] [Google Scholar]
  107. 107.
    Maeda S, Yamamoto H, Kinch LN, Garza CM, Takahashi S, et al. 2020.. Structure, lipid scrambling activity and role in autophagosome formation of ATG9A. . Nat. Struct. Mol. Biol. 27::1194201
    [Crossref] [Google Scholar]
  108. 108.
    Matoba K, Kotani T, Tsutsumi A, Tsuji T, Mori T, et al. 2020.. Atg9 is a lipid scramblase that mediates autophagosomal membrane expansion. . Nat. Struct. Mol. Biol. 27::118593
    [Crossref] [Google Scholar]
  109. 109.
    Orii M, Tsuji T, Ogasawara Y, Fujimoto T. 2021.. Transmembrane phospholipid translocation mediated by Atg9 is involved in autophagosome formation. . J. Cell Biol. 220::e202009194
    [Crossref] [Google Scholar]
  110. 110.
    Chang C, Jensen LE, Hurley JH. 2021.. Autophagosome biogenesis comes out of the black box. . Nat. Cell Biol. 23::45056
    [Crossref] [Google Scholar]
  111. 111.
    Ordureau A, Heo JM, Duda DM, Paulo JA, Olszewski JL, et al. 2015.. Defining roles of PARKIN and ubiquitin phosphorylation by PINK1 in mitochondrial quality control using a ubiquitin replacement strategy. . PNAS 112::663742
    [Crossref] [Google Scholar]
  112. 112.
    Long J, Gallagher TR, Cavey JR, Sheppard PW, Ralston SH, et al. 2008.. Ubiquitin recognition by the ubiquitin-associated domain of p62 involves a novel conformational switch. . J. Biol. Chem. 283::542740
    [Crossref] [Google Scholar]
  113. 113.
    Yoshida Y, Yasuda S, Fujita T, Hamasaki M, Murakami A, et al. 2017.. Ubiquitination of exposed glycoproteins by SCFFBXO27 directs damaged lysosomes for autophagy. . PNAS 114::857479
    [Crossref] [Google Scholar]
  114. 114.
    Teranishi H, Tabata K, Saeki M, Umemoto T, Hatta T, et al. 2022.. Identification of CUL4A-DDB1-WDFY1 as an E3 ubiquitin ligase complex involved in initiation of lysophagy. . Cell Rep. 40::111349
    [Crossref] [Google Scholar]
  115. 115.
    Deshar R, Moon S, Yoo W, Cho EB, Yoon SK, Yoon JB. 2016.. RNF167 targets Arl8B for degradation to regulate lysosome positioning and endocytic trafficking. . FEBS J. 283::458399
    [Crossref] [Google Scholar]
  116. 116.
    Mi N, Chen Y, Wang S, Chen M, Zhao M, et al. 2015.. CapZ regulates autophagosomal membrane shaping by promoting actin assembly inside the isolation membrane. . Nat. Cell Biol. 17::111223
    [Crossref] [Google Scholar]
  117. 117.
    Meyer H, Weihl CC. 2014.. The VCP/p97 system at a glance: connecting cellular function to disease pathogenesis. . J. Cell Sci. 127::387783
    [Google Scholar]
  118. 118.
    Johnson AE, Shu H, Hauswirth AG, Tong A, Davis GW. 2015.. VCP-dependent muscle degeneration is linked to defects in a dynamic tubular lysosomal network in vivo. . eLife 4::e07366
    [Crossref] [Google Scholar]
  119. 119.
    Arhzaouy K, Papadopoulos C, Schulze N, Pittman SK, Meyer H, Weihl CC. 2019.. VCP maintains lysosomal homeostasis and TFEB activity in differentiated skeletal muscle. . Autophagy 15::108299
    [Crossref] [Google Scholar]
  120. 120.
    Klickstein JA, Johnson MA, Antonoudiou P, Maguire J, Paulo JA, et al. 2023.. ALS-related p97 R155H mutation disrupts lysophagy in iPSC-derived motor neurons. . bioRxiv 2023.06.21.545956. https://doi.org/10.1101/2023.06.21.545956
  121. 121.
    Hall EA, Nahorski MS, Murray LM, Shaheen R, Perkins E, et al. 2017.. PLAA mutations cause a lethal infantile epileptic encephalopathy by disrupting ubiquitin-mediated endolysosomal degradation of synaptic proteins. . Am. J. Hum. Genet. 100::70624
    [Crossref] [Google Scholar]
  122. 122.
    Gallagher ER, Holzbaur ELF. 2023.. The selective autophagy adaptor p62/SQSTM1 forms phase condensates regulated by HSP27 that facilitate the clearance of damaged lysosomes via lysophagy. . Cell Rep. 42::112037
    [Crossref] [Google Scholar]
  123. 123.
    Vendredy L, Adriaenssens E, Timmerman V. 2020.. Small heat shock proteins in neurodegenerative diseases. . Cell Stress Chaperones 25::67999
    [Crossref] [Google Scholar]
  124. 124.
    Koerver L, Papadopoulos C, Liu B, Kravic B, Rota G, et al. 2019.. The ubiquitin-conjugating enzyme UBE2QL1 coordinates lysophagy in response to endolysosomal damage. . EMBO Rep. 20::e48014
    [Crossref] [Google Scholar]
  125. 125.
    Liu EA, Schultz ML, Mochida C, Chung C, Paulson HL, Lieberman AP. 2020.. Fbxo2 mediates clearance of damaged lysosomes and modifies neurodegeneration in the Niemann-Pick C brain. . JCI Insight 5::e136676
    [Crossref] [Google Scholar]
  126. 126.
    Deshaies RJ, Joazeiro CA. 2009.. RING domain E3 ubiquitin ligases. . Annu. Rev. Biochem. 78::399434
    [Crossref] [Google Scholar]
  127. 127.
    Sardiello M, Palmieri M, di Ronza A, Medina DL, Valenza M, et al. 2009.. A gene network regulating lysosomal biogenesis and function. . Science 325::47377
    [Crossref] [Google Scholar]
  128. 128.
    Settembre C, Fraldi A, Medina DL, Ballabio A. 2013.. Signals from the lysosome: a control centre for cellular clearance and energy metabolism. . Nat. Rev. Mol. Cell Biol. 14::28396
    [Crossref] [Google Scholar]
  129. 129.
    Medina DL, Di Paola S, Peluso I, Armani A, De Stefani D, et al. 2015.. Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB. . Nat. Cell Biol. 17::28899
    [Crossref] [Google Scholar]
  130. 130.
    Napolitano G, Di Malta C, Esposito A, de Araujo MEG, Pece S, et al. 2020.. A substrate-specific mTORC1 pathway underlies Birt–Hogg–Dubé syndrome. . Nature 585::597602
    [Crossref] [Google Scholar]
  131. 131.
    Petit CS, Roczniak-Ferguson A, Ferguson SM. 2013.. Recruitment of folliculin to lysosomes supports the amino acid-dependent activation of Rag GTPases. . J. Cell Biol. 202::110722
    [Crossref] [Google Scholar]
  132. 132.
    Kumar S, Jain A, Choi SW, da Silva GPD, Allers L, et al. 2020.. Mammalian Atg8 proteins and the autophagy factor IRGM control mTOR and TFEB at a regulatory node critical for responses to pathogens. . Nat. Cell Biol. 22::97385
    [Crossref] [Google Scholar]
  133. 133.
    Xu Y, Zhou P, Cheng S, Lu Q, Nowak K, et al. 2019.. A bacterial effector reveals the V-ATPase-ATG16L1 axis that initiates xenophagy. . Cell 178::55266.e20
    [Crossref] [Google Scholar]
  134. 134.
    Hooper KM, Jacquin E, Li T, Goodwin JM, Brumell JH, et al. 2022.. V-ATPase is a universal regulator of LC3-associated phagocytosis and non-canonical autophagy. . J. Cell Biol. 221::e202105112
    [Crossref] [Google Scholar]
  135. 135.
    Nakamura S, Shigeyama S, Minami S, Shima T, Akayama S, et al. 2020.. LC3 lipidation is essential for TFEB activation during the lysosomal damage response to kidney injury. . Nat. Cell Biol. 22::125263
    [Crossref] [Google Scholar]
  136. 136.
    Goodwin JM, Walkup WG IV, Hooper K, Li T, Kishi-Itakura C, et al. 2021.. GABARAP sequesters the FLCN-FNIP tumor suppressor complex to couple autophagy with lysosomal biogenesis. . Sci. Adv. 7::eabj2485
    [Crossref] [Google Scholar]
  137. 137.
    Luzio JP, Hackmann Y, Dieckmann NM, Griffiths GM. 2014.. The biogenesis of lysosomes and lysosome-related organelles. . Cold Spring Harb. Perspect. Biol. 6::a016840
    [Crossref] [Google Scholar]
  138. 138.
    Yang C, Wang X. 2021.. Lysosome biogenesis: regulation and functions. . J. Cell Biol. 220::e202102001
    [Crossref] [Google Scholar]
  139. 139.
    Yu L, McPhee CK, Zheng L, Mardones GA, Rong Y, et al. 2010.. Termination of autophagy and reformation of lysosomes regulated by mTOR. . Nature 465::94246
    [Crossref] [Google Scholar]
  140. 140.
    Rong Y, Liu M, Ma L, Du W, Zhang H, et al. 2012.. Clathrin and phosphatidylinositol-4,5-bisphosphate regulate autophagic lysosome reformation. . Nat. Cell Biol. 14::92434
    [Crossref] [Google Scholar]
  141. 141.
    Dai A, Yu L, Wang HW. 2019.. WHAMM initiates autolysosome tubulation by promoting actin polymerization on autolysosomes. . Nat. Commun. 10::3699
    [Crossref] [Google Scholar]
  142. 142.
    Bhattacharya A, Mukherjee R, Kuncha SK, Brunstein ME, Rathore R, et al. 2023.. A lysosome membrane regeneration pathway depends on TBC1D15 and autophagic lysosomal reformation proteins. . Nat. Cell Biol. 25::68598
    [Crossref] [Google Scholar]
  143. 143.
    Bonet-Ponce L, Beilina A, Williamson CD, Lindberg E, Kluss JH, et al. 2020.. LRRK2 mediates tubulation and vesicle sorting from lysosomes. . Sci. Adv. 6::eabb2454
    [Crossref] [Google Scholar]
  144. 144.
    Cross J, Durgan J, McEwan DG, Florey O. 2023.. Lysosome damage triggers direct ATG8 conjugation and ATG2 engagement via CASM. . bioRxiv 2023.03.22.533754. https://doi.org/10.1101/2023.03.22.533754
  145. 145.
    Stockwell BR. 2022.. Ferroptosis turns 10: emerging mechanisms, physiological functions, and therapeutic applications. . Cell 185::240121
    [Crossref] [Google Scholar]
  146. 146.
    Bhardwaj M, Lee JJ, Versace AM, Harper SL, Goldman AR, et al. 2023.. Lysosomal lipid peroxidation regulates tumor immunity. . J. Clin. Investig. 133:(8):e164596
    [Crossref] [Google Scholar]
  147. 147.
    Jia J, Wang F, Bhujabal Z, Peters R, Mudd M, et al. 2023.. Membrane Atg8ylation, stress granule formation, and MTOR regulation during lysosomal damage. . Autophagy 19::189395
    [Crossref] [Google Scholar]
  148. 148.
    Costa-Mattioli M, Walter P. 2020.. The integrated stress response: from mechanism to disease. . Science 368::eaat5314
    [Crossref] [Google Scholar]
/content/journals/10.1146/annurev-biochem-030222-102505
Loading
/content/journals/10.1146/annurev-biochem-030222-102505
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error