Cited by 1,735Autophagy in Disease and TherapyMitochondrial Function and PathologyCell death mechanisms and regulation

During autophagy mitochondria elongate, are spared from degradation and sustain cell viability

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Gomes, Ligia C., Benedetto, Giulietta Di, Scorrano, Luca·2011·Nature Cell Biology

Abstract

A plethora of cellular processes, including apoptosis, depend on regulated changes in mitochondrial shape and ultrastructure. The role of mitochondria and of their morphology during autophagy, a bulk degradation and recycling process of eukaryotic cells' constituents, is not well understood. Here we show that mitochondrial morphology determines the cellular response to macroautophagy. When autophagy is triggered, mitochondria elongate in vitro and in vivo. During starvation, cellular cyclic AMP levels increase and protein kinase A (PKA) is activated. PKA in turn phosphorylates the pro-fission dynamin-related protein 1 (DRP1), which is therefore retained in the cytoplasm, leading to unopposed mitochondrial fusion. Elongated mitochondria are spared from autophagic degradation, possess more cristae, increased levels of dimerization and activity of ATP synthase, and maintain ATP production. Conversely, when elongation is genetically or pharmacologically blocked, mitochondria consume ATP, precipitating starvation-induced death. Thus, regulated changes in mitochondrial morphology determine the fate of the cell during autophagy.

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  1. [61]de Brito OM Scorrano L Mitofusin 2 tethers endoplasmic reticulum to mitochondria Nature 2008 456 605 610 19052620

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Authors
Gomes, L. C., Benedetto, G. D., & Scorrano, L.
Affiliations
  • Veneto Institute of Molecular Medicine (IT)
  • University of Geneva (CH)
Corresponding author
Scorrano, Luca
Venue
Nature Cell Biology
Published
2011-04-10
Volume
13
Issue
5
Pages
589-598
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
OpenAlex
W2121077787
Cited by
1,735
References
65
Citations by year
2026: 63 · 2025: 94 · 2024: 120 · 2023: 120 · 2022: 106 · 2021: 145 · 2020: 153 · 2019: 129 · 2018: 116 · 2017: 135 · 2016: 127 · 2015: 89 · 2014: 116 · 2013: 96 · 2012: 96
FWCI
80.40
Type
journal article
Language
en
Open access
Locations
  • Nature Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion)
Funders
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (118171)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
autophagy, mitochondrial morphology, mitochondrial elongation, mitochondrial fusion, Drp1, protein kinase A, cyclic AMP, starvation, ATP synthase, ATP production, mitochondrial cristae, cell viability
MeSH terms
Adenosine Triphosphate, Animals, Autophagy, Cell Line, Humans, Mitochondria, Cell Death, Mice

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