RRC ID 59501
Author Haeussler S, Köhler F, Witting M, Premm MF, Rolland SG, Fischer C, Chauve L, Casanueva O, Conradt B.
Title Autophagy compensates for defects in mitochondrial dynamics.
Journal PLoS Genet
Abstract Compromising mitochondrial fusion or fission disrupts cellular homeostasis; however, the underlying mechanism(s) are not fully understood. The loss of C. elegans fzo-1MFN results in mitochondrial fragmentation, decreased mitochondrial membrane potential and the induction of the mitochondrial unfolded protein response (UPRmt). We performed a genome-wide RNAi screen for genes that when knocked-down suppress fzo-1MFN(lf)-induced UPRmt. Of the 299 genes identified, 143 encode negative regulators of autophagy, many of which have previously not been implicated in this cellular quality control mechanism. We present evidence that increased autophagic flux suppresses fzo-1MFN(lf)-induced UPRmt by increasing mitochondrial membrane potential rather than restoring mitochondrial morphology. Furthermore, we demonstrate that increased autophagic flux also suppresses UPRmt induction in response to a block in mitochondrial fission, but not in response to the loss of spg-7AFG3L2, which encodes a mitochondrial metalloprotease. Finally, we found that blocking mitochondrial fusion or fission leads to increased levels of certain types of triacylglycerols and that this is at least partially reverted by the induction of autophagy. We propose that the breakdown of these triacylglycerols through autophagy leads to elevated metabolic activity, thereby increasing mitochondrial membrane potential and restoring mitochondrial and cellular homeostasis.
Volume 16(3)
Pages e1008638
Published 2020-3-1
DOI 10.1371/journal.pgen.1008638
PMID 32191694
PMC PMC7135339
MeSH Animals Autophagy / genetics* Autophagy / physiology Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism GTP Phosphohydrolases / genetics GTP Phosphohydrolases / metabolism Gene Expression Regulation / genetics Homeostasis / genetics Membrane Potential, Mitochondrial / genetics Membrane Potential, Mitochondrial / physiology Mitochondria / genetics* Mitochondrial Dynamics / genetics Mitochondrial Proteins / genetics RNA Interference Unfolded Protein Response / genetics* Unfolded Protein Response / physiology
IF 5.224
Times Cited 1
C.elegans tm1133 tm1108 tm4525