Machinery, regulation and pathophysiological implications of autophagosome maturation.
Journal
Nature reviews. Molecular cell biology
ISSN: 1471-0080
Titre abrégé: Nat Rev Mol Cell Biol
Pays: England
ID NLM: 100962782
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
accepted:
17
06
2021
pubmed:
25
7
2021
medline:
26
11
2021
entrez:
24
7
2021
Statut:
ppublish
Résumé
Autophagy is a versatile degradation system for maintaining cellular homeostasis whereby cytosolic materials are sequestered in a double-membrane autophagosome and subsequently delivered to lysosomes, where they are broken down. In multicellular organisms, newly formed autophagosomes undergo a process called 'maturation', in which they fuse with vesicles originating from endolysosomal compartments, including early/late endosomes and lysosomes, to form amphisomes, which eventually become degradative autolysosomes. This fusion process requires the concerted actions of multiple regulators of membrane dynamics, including SNAREs, tethering proteins and RAB GTPases, and also transport of autophagosomes and late endosomes/lysosomes towards each other. Multiple mechanisms modulate autophagosome maturation, including post-translational modification of key components, spatial distribution of phosphoinositide lipid species on membranes, RAB protein dynamics, and biogenesis and function of lysosomes. Nutrient status and various stresses integrate into the autophagosome maturation machinery to coordinate the progression of autophagic flux. Impaired autophagosome maturation is linked to the pathogenesis of various human diseases, including neurodegenerative disorders, cancer and myopathies. Furthermore, invading pathogens exploit various strategies to block autophagosome maturation, thus evading destruction and even subverting autophagic vacuoles (autophagosomes, amphisomes and autolysosomes) for survival, growth and/or release. Here, we discuss the recent progress in our understanding of the machinery and regulation of autophagosome maturation, the relevance of these mechanisms to human pathophysiology and how they are harnessed by pathogens for their benefit. We also provide perspectives on targeting autophagosome maturation therapeutically.
Identifiants
pubmed: 34302147
doi: 10.1038/s41580-021-00392-4
pii: 10.1038/s41580-021-00392-4
pmc: PMC8300085
doi:
Substances chimiques
SNARE Proteins
0
rab GTP-Binding Proteins
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
733-750Informations de copyright
© 2021. Springer Nature Limited.
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