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During Autophagy Mitochondria Elongate, Are Spared from Degradation and Sustain Cell Viability

Overview
Journal Nat Cell Biol
Specialty Cell Biology
Date 2011 Apr 12
PMID 21478857
Citations 870
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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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References
1.
Braschi E, Zunino R, McBride H . MAPL is a new mitochondrial SUMO E3 ligase that regulates mitochondrial fission. EMBO Rep. 2009; 10(7):748-54. PMC: 2727426. DOI: 10.1038/embor.2009.86. View

2.
Song Z, Chen H, Fiket M, Alexander C, Chan D . OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L. J Cell Biol. 2007; 178(5):749-55. PMC: 2064540. DOI: 10.1083/jcb.200704110. View

3.
Zheng Y, Shahnazari S, Brech A, Lamark T, Johansen T, Brumell J . The adaptor protein p62/SQSTM1 targets invading bacteria to the autophagy pathway. J Immunol. 2009; 183(9):5909-16. DOI: 10.4049/jimmunol.0900441. View

4.
Rich P . Chemiosmotic coupling: The cost of living. Nature. 2003; 421(6923):583. DOI: 10.1038/421583a. View

5.
Tondera D, Grandemange S, Jourdain A, Karbowski M, Mattenberger Y, Herzig S . SLP-2 is required for stress-induced mitochondrial hyperfusion. EMBO J. 2009; 28(11):1589-600. PMC: 2693158. DOI: 10.1038/emboj.2009.89. View