The coming of age of chaperone-mediated autophagy
By Susmita Kaushik, A. Cuervo. Nature reviews. Molecular cell biology, 2018
1,178 citations recorded by the source corpus.
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. The selective degradation of cellular components via chaperone-mediated autophagy (CMA) functions to regulate a wide range of cellular processes, from metabolism to DNA repair and cellular reprogramming. Recent in vivo studies have enabled to dissect key roles of CMA in ageing and ageing-associated disorders such as cancer and neurodegeneration.
Subfields: Cell Biology, Epidemiology, Geriatrics and Gerontology
View Paper: https://www.semanticscholar.org/paper/7e25c32a9c719905c145ab2e96d5007f43e008d7
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Citations in the corpus
- Ferroptosis in cancer: from molecular mechanisms to therapeutic strategies (2024, background): “274 GPX4, a common substrate protein, undergoes CMA degradation facilitated by heat shock cognate 71 kDa protein (HSC70) and heat shock protein 90 (HSP90), enhancing the sensitivity of tumor cells to ferroptosis.”
- Autophagy-Independent Functions of the Autophagy Machinery (2019, background): “…of the lysosomal membrane, and (2) chaperone-medicated autophagy (CMA), which reliesona specific splicing isoformof lysosomal-associatedmembrane protein 2 (LAMP2) as a translocase for KFERQ-containing cytosolic proteins into the lysosomal lumen (Kaushik and Cuervo, 2018; Li et al., 2012a).”
- Measuring biological aging in humans: A quest (2019, background): “…complex goals are accomplished through different mechanisms, such as chaperon-dependent and chaperonindependent autophagy, as well as protein biogenesis, folding, trafficking, and degradation (including proteasomal degradation; Kaushik & Cuervo, 2018; Morimoto & Cuervo, 2014; Wong & Cuervo, 2010).”
- Autophagy in Human Diseases. (2020, background): “translocons deliver unfolded proteins into the lumen of lysosomes.(9) Cyto-”
- Targeted protein degradation: mechanisms, strategies and application (2022, background): “Second, the formation of autophagosomes is unnecessary in CMA.78 With the intensive research in the endosome-lysosome and autophagosome-lysosome degradation pathways, TPD strategies via the lysosomal pathway, such as LYTAC, AbTAC, ATTEC, AUTAC, bispecific aptamer chimeras, and AUTOTAC have emerged i”
- Recent advances in Alzheimer’s disease: mechanisms, clinical trials and new drug development strategies (2024, background): “220,223,224 226 Macroautophagy, the main subtype, is primarily regulated by mTORC1 for activating the unc-51-like autophagy activating kinase 1 (ULK1) complex and dephosphor-ylating transcription factor EB (TFEB) to induce autophagy.”
- Autophagy in inflammation, infection, and immunometabolism (2021, background): “Finally, a process of individual protein import across lysosomal membrane for digestion, referred to as chaperone-mediated autophagy (Kaushik and Cuervo, 2018), affects immune cells (Macian, 2019; Valdor et al.”