Autophagy is a recycling program that maintains quality control inside cells. The term 'autophagy' - derived from the Greek words auto-, meaning 'self', and pagein, meaning 'to eat' - refers to the degradation of cellular components by lysosomes. Mammalian cells have three types autophagy – macroautophagy, microautophagy, and chaperone-mediated autophagy that differ in the type of cargo degraded and how the cargo is delivered to the lysosomes. Chaperone-mediated autophagy (CMA) is the selective degradation of proteins by lysosomes. Dr. Kaushik’s current research interests lie in the role of chaperone-mediated autophagy (CMA) in regulating lipid metabolism. Specifically, a) how CMA manages the formation and the utilization of fat stores, and b) how dysregulation of CMA (in aging) could lead to perturbations in lipohomeostasis observed as we age. Dr. Kaushik's interests are also focused on understanding the mechanisms causing lysosomal disorders and her efforts are currently directed towards NGLY1 deficiency, a rare genetic disorder. 

:: Research Papers

Jafari M, Macho-González A, Diaz A, Lindenau K, Santiago-Fernández O, Zeng M, Massey AC, de Cabo R, Kaushik S, Cuervo AM.  

Calorie restriction and calorie-restriction mimetics activate chaperone-mediated autophagy.  

Proc Natl Acad Sci USA. 2024; 121: e2317945121. PMID: 38889154.

Manole A, Wong T, Rhee A, Novak S, Chin SM, Tsimring K, Paucar A, Williams A, Newmeyer TF, Schafer ST, Rosh I, Kaushik S, Hoffman R, Chen S, Wang G, Snyder M, Cuervo AM, Andrade L, Manor U, Lee K, Jones JR, Stern S, Marchetto MC, Gage FH. 

NGLY1 mutations cause protein aggregation in human neurons. 

Cell Rep. 2023; 42: 113466. PMID: 38039131.

Li J, Krause GJ, Gui Q, Kaushik S, Rona G, Zhang Q, Liang FX, Dhabaria A, Anerillas C, Martindale JL, Vasilyev N, Askenazi M, Ueberheide B, Nudler E, Gorospe M, Cuervo AM, Pagano M. 

A noncanonical function of SKP1 regulates the switch between autophagy and unconventional secretion. 

Sci Adv. 2023; 9: eadh1134. PMID: 37831778.

Kaushik S, Juste YR, Lindenau K, Dong S, Macho-González A, Santiago-Fernández O, McCabe M, Singh R, Gavathiotis E, Cuervo AM. 

Chaperone-mediated autophagy regulates adipocyte differentiation. 

Sci Adv. 2022; 8: eabq2733. PMID: 36383673.

Madrigal-Matute J, de Bruijn J, van Kuijk K, Riascos-Bernal DF, Diaz A, Tasset I, Martín-Segura A, Gijbels MJJ, Sander B, Kaushik S, Biessen EAL, Tiano S, Bourdenx M, Krause GJ, McCracken I, Baker AH, Jin H, Sibinga NES, Bravo-Cordero JJ, Macian F, Singh R, Rensen PCN, Berbée JFP, Pasterkamp G, Sluimer JC, Cuervo AM.
Protective role of chaperone-mediated autophagy against atherosclerosis.
Proc Natl Acad Sci U S A. 2022; 119: e2121133119. PMID: 35363568

Juste YR*, Kaushik S*, Bourdenx M, Aflakpui R, Bandyopadhyay S, Garcia F, Diaz A, Lindenau K, Tu V, Krause GJ, Jafari M, Singh R, Muñoz J, Macian F, Cuervo AM.
Reciprocal regulation of chaperone-mediated autophagy and the circadian clock.
Nat Cell Biol. 2021 Dec 7. Epub ahead of print. PMID: 34876687 *equal contribution   +Featured: News & Views, Nat Cell Biol

Bourdenx M, Martin-Segura A, Scrivo A, Rodriguez-Navarro JA, Kaushik S, Tasset I, Diaz A, Storm NJ, Xin Q, Juste YR, Stevenson E, Luengo E, Clement CC, Choi SJ, Krogan NJ, Mosharov EV, Santambrogio L, Grueninger F, Collin L, Swaney DL, Sulzer D, Gavathiotis E, Cuervo AM.
Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome.
Cell. 2021; 184: 2696-2714. PMID: 33891876

Dong S, Wang Q, Kao YR, Diaz A, Tasset I, Kaushik S, Thiruthuvanathan V, Zintiridou A, Nieves E, Dzieciatkowska M, Reisz JA, Gavathiotis E, D'Alessandro A, Will B, Cuervo AM.
Chaperone-mediated autophagy sustains haematopoietic stem--cell function.
Nature. 2021; 591: 117-23. PMID: 33442062

Schultz M, Krus K, Kaushik S, Dang D, Chopra R, Qi L, Shakkottai V, Cuervo AM, Lieberman A.
Coordinate regulation of mutant NPC1 degradation by selective ER autophagy and MARCH6-dependent ERAD.
Nat Commun. 2018; 9: 3671. PMID: 30202070

Amengual J, Guo L, Strong A, Madrigal-Matute J, Wang H, Kaushik S, Brodsky JL, Rader DJ, Cuervo AM, Fisher EA.
Autophagy is required for sortilin-mediated degradation of apolipoprotein B100. 
Circ Res. 2018; 122: 568-82. PMID: 29301854

Mitchell SJ, Madrigal-Matute J, Scheibye-Knudsen M, Fang E, Aon M, González-Reyes JA, Cortassa S, Kaushik S, Gonzalez-Freire M, Patel B, Wahl D, Ali A, Calvo-Rubio M, Burón MI, Guiterrez V, Ward TM, Palacios HH, Cai H, Frederick DW, Hine C, Broeskamp F, Habering L, Dawson J, Beasley TM, Wan J, Ikeno Y, Hubbard G, Becker KG, Zhang Y, Bohr VA, Longo DL, Navas P, Ferrucci L, Sinclair DA, Cohen P, Egan JM, Mitchell JR, Baur JA, Allison DB, Anson RM, Villalba JM, Madeo F, Cuervo AM, Pearson KJ, Ingram DK, Bernier M, de Cabo R.
Effects of sex, strain, and energy intake on hallmarks of aging in mice.
Cell Metab. 2016; 23: 1093-112. PMID: 27304509 + F1000 Prime recommended 

Morozova K, Clement CC, Kaushik S, Stiller B, Arias E, Ahmad A, Rauch JN, Chatterjee V, Melis C, Scharf B, Gestwicki JE, Cuervo AM, Zuiderweg ER, Santambrogio L.
Hsc-70 structural and biological interaction with phosphatidylserine in endosomal microautophagy. 
J Biol Chem. 2016; 291: 18096-106. PMID: 27405763

Kaushik S, Cuervo AM.
AMPK-dependent phosphorylation of lipid droplet protein PLIN2 triggers its degradation by CMA.
Autophagy. 2016; 12: 432-8. PMID: 26902588

Kaushik S, Cuervo AM.
Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy facilitates lipolysis. 
Nat Cell Biol. 2015; 17: 759-70. PMID: 25961502 + F1000 Prime recommended   + Featured: Preview, Cell Metab   + Featured in communication media: Bioportfolio

Rodriguez-Navarro JA, Kaushik S, Koga H, Dall'Armi C, Shui G, Wenk MR, Di Paolo G, Cuervo AM.
Inhibitory effect of dietary lipids on chaperone-mediated autophagy.
Proc Natl Acad Sci USA. 2012; 109: E705-14. PMID: 22331875 + F1000 Prime recommended 

Kaushik S*, Arias E*, Kwon H, Lopez NM, Athonvarangkul D, Sahu S, Schwartz GJ, Pessin JE, Singh R.
Loss of autophagy in hypothalamic POMC neurons impairs lipolysis. 
EMBO Rep. 2012; 13: 258-65. PMID: 22249165 *equal contribution  + F1000 Prime recommended   + Issue Cover   + Featured: Hot off the Press, EMBO Rep

Kaushik S, Rodriguez-Navarro JA, Arias E, Kiffin R, Sahu S, Schwartz GJ, Cuervo AM, Singh R.
Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance.
Cell Metab. 2011; 14: 173-83. PMID: 21803288 + F1000 Prime recommended    + Featured: Research Highlights, Nat Med   + Media coverage: Eureka Alert, Jay Leno Show, LA Times, National Public Radio, Scientist Magazine 

Sahu R, Kaushik S, Clement CC, Cannizzo ES, Scharf B, Follenzi A, Potolicchio I, Nieves E, Cuervo AM, Santambrogio L.
Microautophagy of cytosolic proteins by late endosomes.
Dev Cell. 2011; 20: 131-9. PMID: 21238931 + Featured: Preview, Dev Cell   + Featured: Research Highlight, Nat Rev Mol Cell Biol

Yang DS, Stavrides P, Mohan PS, Kaushik S, Kumar A, Ohno M, Schmidt SD, Wesson D, Bandyopadhyay U, Jiang Y, Pawlik M, Peterhoff CM, Yang AJ, Wilson DA, St George-Hyslop P, Westaway D, Mathews PM, Levy E, Cuervo AM, Nixon RA.
Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer’s disease ameliorates amyloid pathologies and memory deficits.
Brain. 2011; 134: 258-77. PMID: 21186265

Bandyopadhyay U, Sridhar S, Kaushik S, Kiffin R, Cuervo AM.
Identification of regulators of chaperone-mediated autophagy.
Mol Cell. 2010; 39: 535-47. PMID: 20797626 + F1000 Prime recommended

Rothenberg C, Srinivasan D, Mah L, Kaushik S, Peterhoff CM, Ugolino J, Fang S, Cuervo AM, Nixon RA, Monteiro MJ.
Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy.
Hum Mol Genet. 2010; 19: 3219-32. PMID: 20529957

Martinez-Vicente M, Talloczy Z, Wong E, Tang G, Koga H, Kaushik S, de Vries R, Arias E, Harris S, Sulzer D, Cuervo AM.
Cargo recognition failure is responsible for inefficient autophagy in Huntington’s disease.
Nat Neurosci. 2010; 13: 567-76. PMID: 20383138 + F1000 Prime recommended   + Featured: Leading Edge, Cell   + Featured: Research Highlight, Nat Rev Neurol

Koga H, Kaushik S, Cuervo AM.
Altered lipid content inhibits autophagic vesicular fusion.
FASEB J. 2010; 24: 3052-65. PMID: 20375270 

Singh R*, Kaushik S*, Wang Y, Xiang Y, Novak I, Komatsu M, Tanaka K, Cuervo AM, Czaja MJ.
Autophagy regulates lipid metabolism.
Nature. 2009; 458: 1131-5. PMID: 19339967 *equal contribution + F1000 Prime recommended   + Featured: News & Views, Nature   + Featured: Preview, Dev Cell   + Media coverage: ABC, BBC, Discover Magazine, Science Central, Science Daily, Washington Post 

Wang Y, Singh R, Massey AC, Kane SS, Kaushik S, Grant T, Xiang Y, Cuervo AM, Czaja MJ.
Loss of macroautophagy promotes or prevents fibroblast apoptosis depending on the death stimulus.
J Biol Chem. 2008; 283: 4766-77. PMID: 18073215 + J Biol Chem: Paper of the Week   + Issue Cover

Bandyopadhyay U, Kaushik S, Varticovski L, Cuervo AM.
The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane.
Mol Cell Biol. 2008; 28: 5747-63. PMID: 18644871

Kaushik S, Massey AC, Mizushima N, Cuervo AM.
Constitutive activation of chaperone-mediated autophagy in cells with impaired macroautophagy.
Mol Biol Cell. 2008; 19: 2179-92. PMID: 18337468

Martinez-Vicente M, Talloczy Z, Kaushik S, Massey AC, Mazzulli J, Mosharov EV, Hodara R, Fredenburg R, Wu DC, Follenzi A, Dauer W, Przedborski S, Ischiropoulos H, Lansbury PT, Sulzer D, Cuervo AM.
Dopamine-modified alpha-synuclein blocks chaperone-mediated autophagy.
J Clin Invest. 2008; 118: 777-88. PMID: 18172548 + F1000 Prime recommended   + Media coverage: NINDS news, Reuters, Science Daily

Kiffin R*, Kaushik S*, Zeng M, Bandyopadhyay U, Zhang C, Massey AC, Martinez-Vicente M, Cuervo AM.
Altered dynamics of the lysosomal receptor for chaperone-mediated autophagy with age.
J Cell Sci. 2007; 120: 782-91. PMID: 17284523 *equal contribution

Massey AC, Kaushik S, Sovak G, Kiffin R, Cuervo AM.
Consequences of the selective blockage of chaperone-mediated autophagy.
Proc Natl Acad Sci USA. 2006; 103: 5805-10. PMID: 16585521 + F1000 Prime recommended

Kaushik S, Massey AC, Cuervo AM.
Lysosome membrane lipid microdomains: novel regulators of chaperone-mediated autophagy.
EMBO J. 2006; 25: 3921-33. PMID: 16917501 + Selected: Autophagy Section of ASCB Image and Video Library

:: Review Articles 

Kaushik S, Tasset I, Arias E, Pampliega O, Wong E, Martinez-Vicente M, Cuervo AM.
Autophagy and the hallmarks of aging.
Ageing Res Rev. 2021; 72: 101468. PMID: 34563704 + Part of special issue: Women in Aging Research

Klionsky DJ, ... Kaushik S, ... et al.
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). 
Autophagy. 2021; 17: 1-382. PMID: 33634751

Kaushik S, Cuervo AM.
The coming of age of chaperone-mediated autophagy.
Nat Rev Mol Cell Biol. 2018; 19: 365-81. PMID: 29626215  

Kaushik S, Cuervo AM.
Proteostasis and aging.
Nat Med. 2015; 21: 1406-15. PMID: 26646497 + Issue Cover

Kaushik S, Cuervo AM.
Chaperone-mediated autophagy: a unique world to enter the lysosome world.
Trends Cell Biol. 2012; 22: 407-17. PMID: 22748206 + Issue Cover

Kaushik S, Bandyopadhyay U, Sridhar S, Kiffin R, Martinez-Vicente M, Kon M, Orenstein SJ, Wong E, Cuervo AM.
Chaperone-mediated autophagy at a glance.
J Cell Sci. 2011; 124: 495-9. PMID: 21282471

Kaushik S, Cuervo AM.
Methods to monitor chaperone-mediated autophagy.
Methods Enzymol. 2009; 452: 297-324. PMID: 19200890

For complete list: MYNCBI