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

By Lígia C. Gomes, Giulietta Di Benedetto, L. Scorrano. Nature Cell Biology, 2011

1,704 citations recorded by the source corpus.

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.

Subfields: Cell Biology, Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/67a283deff2a4432a45ddfeaef364da3d229a8e1

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

In Epidemiology

In Molecular Biology

Citations in the corpus

Mitochondrial Cristae: Where Beauty Meets Functionality. (2016, background): “For example, activation of the recycling autophagy pathway triggers mitochondrial elongation [2,3], protecting mitochondria from degradation and promoting mitochondrial ATP production to increase the efficiency of energy conversion during nutrient deprivation [2].”
Mitochondria and Mitophagy: The Yin and Yang of Cell Death Control (2012, background): “hyperfused mitochondrial networks that protect mitochondria from elimination by autophagosomes.(152,153) An alternative”
Metabolic regulation of mitochondrial dynamics (2016, background): “Negative regulation of Drp1 by phosphorylation at S637 also occurs during mTOR inhibition and nitrogen starvation, which increases cAMP levels and activates PKA (Gomes et al., 2011; Rambold et al., 2011).”
Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy and mitochondrial fusion dynamics (2015, background): “Monitoring mitochondria and the distribution of FAs delivered into them in starved cells further revealed that mitochondria were highly fused and that FAs were homogenously distributed throughout the mitochondria (Figures 5A and 5D) (Gomes et al., 2011; Rambold et al., 2011).”
Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation (2011, background): “Very recently, nutrient starvation was shown to induce mitochondrial elongation and to protect mitochondria from autophagic degradation (24).”
Mechanisms of mitochondrial fission and fusion. (2013, background): “Low levels of stress are seen with starvation, during which mitochondrial fission is inhibited to protect cells from excessive autophagosomal degradation of mitochondria (Gomes et al. 2011; Rambold et al. 2011).”
Molecular definitions of autophagy and related processes (2017, neutral): “Indeed, mitophagy (see below for a definition) is arguably the best-characterized form of selective macroautophagy (at least in mammalian cells), but parts of the mitochondrial network are also degraded in the course of macroautophagic responses driven by bioenergetic needs (Gomes et al , 2011a,b).”