Role of SUV3 Helicase in Maintaining Mitochondrial Homeostasis in Human Cells

Lily Khidr, Guikai Wu, Antonio Davila, Vincent Procaccio, Douglas Wallace, Wen-Hwa Lee
2008 Journal of Biological Chemistry  
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
more » ... A 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. Prokaryotes and eukaryotes both utilize RNA processing and degradation, albeit via different pathways, as one mechanism for controlling gene expression (1-4) . The RNA degradosome of Escherichia coli, yeast, and mammalian cells have all conserved the ability to turnover RNA; however, the assembly of their multicomponent machineries differ (5, 6). In E. coli, RNA degradation is conducted by the cooperation of four principal enzymes (7). The first enzyme is an endoribonuclease, RNase E, . 3 The abbreviations used are: PNPase, polynucleotide polymerase; shRNA, small hairpin RNA; RNAi, RNA interference; siRNA, small interfering RNA; OXPHOS, oxidative phosphorylation; PBS, phosphate-buffered saline; DAPI, 4Ј,6-diamidino-2-phenylindole; ROS, reactive oxygen species; mtEXO, mitochondrial RNA degradosome.
doi:10.1074/jbc.m802991200 pmid:18678873 pmcid:PMC2556002 fatcat:pqnuetkizbgzbfasggybyhubqa