TitleThe coming of age of chaperone-mediated autophagy.
Publication TypeJournal Article
Year of Publication2018
AuthorsKaushik S, Cuervo AMaria
JournalNat Rev Mol Cell Biol
Volume19
Issue6
Pagination365-381
Date Published2018 Jun
ISSN1471-0080
Abstract

Chaperone-mediated autophagy (CMA) was the first studied process that indicated that degradation of intracellular components by the lysosome can be selective - a concept that is now well accepted for other forms of autophagy. Lysosomes can degrade cellular cytosol in a nonspecific manner but can also discriminate what to target for degradation with the involvement of a degradation tag, a chaperone and a sophisticated mechanism to make the selected proteins cross the lysosomal membrane through a dedicated translocation complex. Recent studies modulating CMA activity in vivo using transgenic mouse models have demonstrated that selectivity confers on CMA the ability to participate in the regulation of multiple cellular functions. Timely degradation of specific cellular proteins by CMA modulates, for example, glucose and lipid metabolism, DNA repair, cellular reprograming and the cellular response to stress. These findings expand the physiological relevance of CMA beyond its originally identified role in protein quality control and reveal that CMA failure with age may aggravate diseases, such as ageing-associated neurodegeneration and cancer.

DOI10.1038/s41580-018-0001-6
Alternate JournalNat. Rev. Mol. Cell Biol.
PubMed ID29626215
Grant ListU54 NS100717 / NS / NINDS NIH HHS / United States
R01 AG021904 / AG / NIA NIH HHS / United States
R37 AG021904 / AG / NIA NIH HHS / United States
RF1 AG054108 / AG / NIA NIH HHS / United States
R01 DK098408 / DK / NIDDK NIH HHS / United States
P01 AG031782 / AG / NIA NIH HHS / United States