During autophagy mitochondria elongate, are spared from degradation and sustain cell viability
Open accessAbstract
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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Twelve h of fasting in mice may be sufficient to trigger autophagy in muscle, but the appropriate time should be determined empirically.
“Twelve h of fasting in mice may be sufficient to trigger autophagy in muscle, 639,640 but the appropriate time should be determined empirically.”
From Guidelines for the use and interpretation of assays for monitoring autophagy (2012) · cites this paper as [639]
Mitochondrial fusion enables redistribution of energy in the form of mitochondrial potential, metabolites, proteins, and mtDNA, improving calcium handling and ATP synthesis.
“This process enables the redistribution of energy in the form of mitochondrial potential, metabolites, proteins, and mtDNA, improving calcium handling, and ATP synthesis [24, 54–57].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [55]
Mdivi-1 or rotenone induced perinuclear accumulation of damaged mitochondria.
“This is corroborated by our findings that either Mdivi-1 (mitophagy inhibitor) (49) or rotenone (increasing mtROS generation) (35) induced perinuclear accumulation of damaged mitochondria and cellular senescence.”
From Impaired mitophagy leads to cigarette smoke stress‐induced cellular senescence: implications for chronic obstructive pulmonary disease (2015) · cites this paper as [49]
Impaired mitophagy occurs during mitochondrial elongation.
“These results are in agreement with the previous reports showing impaired mitophagy occurring during mitochondrial elongation (49).”
From Impaired mitophagy leads to cigarette smoke stress‐induced cellular senescence: implications for chronic obstructive pulmonary disease (2015) · cites this paper as [49]
Mdivi-1 or rotenone induced cellular senescence.
“This is corroborated by our findings that either Mdivi-1 (mitophagy inhibitor) (49) or rotenone (increasing mtROS generation) (35) induced perinuclear accumulation of damaged mitochondria and cellular senescence.”
From Impaired mitophagy leads to cigarette smoke stress‐induced cellular senescence: implications for chronic obstructive pulmonary disease (2015) · cites this paper as [49]
Cells under a well-fed condition maintain their mitochondria in a separated or fragmented state, while under fasting or starved conditions mitochondria tend to persist in a connected or fused state.
“Cells under a well-fed condition maintain their mitochondria in a separated (or fragmented) state, while under fasting or starved conditions, mitochondria tend to persist in a connected (or fused) state (Gomes et al, 2011).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Gomes et al, 2011
Changes in mitochondrial architecture can affect respiratory complex assembly and the proper coupling of respiration to ATP synthesis.
“Indeed, as described below, changes in mitochondrial architecture can affect respiratory complex assembly and the proper coupling of respiration to ATP synthesis (Gomes et al, 2011).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Gomes et al, 2011
Elongated mitochondria upon fasting possess more cristae and increased levels of dimerization and activity of ATP synthase, ensuring a better coupling of fuel oxidation with ATP synthesis.
“Elongated mitochondria upon fasting possess more cristae and increased levels of dimerization and activity of ATP synthase, ensuring a better coupling of fuel oxidation with ATP synthesis (Gomes et al, 2011).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Gomes et al, 2011
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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
- PMC
- PMC3088644
- 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
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- 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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