Our research

IN AUTOPHAGY IT IS ALL ABOUT SELECTIVITY

The main focus of our laboratory is to understand how cytosolic proteins are transported into lysosomes for their degradation (autophagy) and how impaired autophagy contributes to aging and age-related diseases. A common feature of senescent cells is the accumulation of abnormal or damaged proteins in their cytosol that, undoubtedly, impairs cellular function. Protein accumulation results, at least in part, from impaired protein degradation with age. Among the different systems that participate in the intracellular degradation of proteins, lysosomes are the most affected by age. We have previously identified in many tissues of aged animals a decrease with age in the activity of a selective pathway for the degradation of cytosolic proteins in lysosomes known as chaperone-mediated autophagy. The main goal of our research is to identify the defect(s) that lead to the decreased activity of selective forms of autophagy with age and in age related pathologies, and to analyze if the correction of those defects and recovery of normal proteolytic activity in old cells leads to an improvement in cellular function.

  • Chaperone-mediated autophagy sustains haematopoietic stem-cell function. 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. Nature, 2021. doi: 10.1038/s41586-020-03129-z

  • Monitoring spatiotemporal changes in chaperone-mediated autophagy in vivo. Dong S, Aguirre-Hernandez C, Scrivo A, Eliscovich C, Arias E, Bravo-Cordero JJ, Cuervo AM. Nature Comm, 2020. doi: 10.1038/s41467-019-14164-4

  • Proteome-wide analysis of chaperone-mediated autophagy targeting motifs. Kirchner P, Bourdenx M, Madrigal-Matute J, Tiano S, Diaz A, Barholdy BA, Will B, Cuervo A. PLoS Biology, 2019 doi: 10.1371/journal.pbio.3000301

  • The coming of age of chaperone-mediated autophagy. Kaushik K, Cuervo AM. Nat Rev Cell Mol Biol, 2018. doi: 10.1038/s41580-018-0001-6

  • Humanin is an endogenous activators of chaperone-mediated autophagy. Gong Z, Tasset I, Diaz A, Anguiano J, Tas E, Cui L, Kuliawat R, Liu H, Kuhn B, Cuervo AM, Muzumdar R. J Cell Biol, 2018. doi: 10.1083/jcb.201606095

  • Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy facilitates lipolysis. Kaushik, S. Cuervo AM. Nat Cell Biol, 2015. doi: 10.1038/ncb3166

  • Regulated degradation of Chk1 by chaperone-mediated autophagy in response to DNA damage. Park C, Shu Y, Cuervo AM. Nat Commun, 2015. doi: 10.1038/ncomms7823

  • Lysosomal mTORC2/PHLPP1/Akt regulate chaperone-mediated autophagy. Arias E., Koga H, Diaz A, Mocholi E, Patel B, Cuervo AM. Mol Cell, 2015. doi: 10.1016/j.molcel.2015.05.030

  • Functional interaction between autophagy and ciliogenesis. Pampliega O, Orhon I, Patel B, Sridhar S, Diaz-Carretero A, Beau I, Codogno P, Satir B, Satir P, Cuervo AM. Nature, 2013. doi: 10.1038/nature12639

  • Chemical modulation of chaperone-mediated autophagy by novel retinoic acid derivatives. Anguiano J, Gaerner T, Daas B, Gavathiotis E, Cuervo AM. Nat Chem Biol, 2013. doi: 10.1038/nchembio.1230

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