Role of SUV3 helicase in maintaining mitochondrial homeostasis in human cells.
In yeast mitochondria, RNA degradation takes place through the coordinated activities of ySuv3 helicase and yDss1 exoribonuclease (mtEXO), whereas in bacteria, RNA is degraded via RNaseE, RhlB, PNPase, and enolase. Yeast lacking the Suv3 component of the mtEXO form petits and undergo a toxic accumulation of omega intron RNAs. Mammalian mitochondria resemble their prokaryotic origins by harboring a polyadenylation-dependent RNA degradation mechanism, but whether SUV3 participates in regulating RNA turnover in mammalian mitochondria is unclear. We found that lack of hSUV3 in mammalian cells subsequently yielded an accumulation of shortened polyadenylated mtRNA species and impaired mitochondrial protein synthesis. This suggests that SUV3 may serve in part as a component of an RNA degradosome, resembling its yeast ancestor. Reduction in the expression levels of oxidative phosphorylation components correlated with an increase in reactive oxygen species generation, whereas membrane potential and ATP production were decreased. These cumulative defects led to pleiotropic effects in mitochondria such as decreased mtDNA copy number and a shift in mitochondrial morphology from tubular to granular, which eventually manifests in cellular senescence or cell death. Thus, our results suggest that SUV3 is essential for maintaining proper mitochondrial function, likely through a conserved role in mitochondrial RNA regulation.
Khidr
Lily
L
Department of Biological Chemistry, School of Medicine, University of California, Irvine, California 92697, USA.
Wu
Guikai
G
Davila
Antonio
A
Procaccio
Vincent
V
Wallace
Douglas
D
Lee
Wen-Hwa
WH
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000096:biosynthesis; D010085:Oxidative Phosphorylation; D014176:Protein Biosynthesis / Q000502:physiology; D012313:RNA / Q000378:metabolism*; D020871:RNA Stability / Q000502:physiology*; D000077278:RNA, Mitochondrial
D024101:Mitochondrial Proteins; D000077278:RNA, Mitochondrial; D012313:RNA; D000255:Adenosine Triphosphate; C469673:SUPV3L1 protein, human; D053487:DEAD-box RNA Helicases