Mitochondrial CLPP2 Assists Coordination and Homeostasis of Respiratory Complexes
Jakob Petereit, Owen Duncan, Monika W. Murcha, Ricarda Fenske, Emilia Cincu, Jonathan Cahn, Adriana Pružinská, Aneta Ivanova, Laxmikanth Kollipara, Stefanie Wortelkamp, Albert Sickmann, Jiwon Lee, Ryan Lister, A. Harvey Millar, Shaobai Huang
Abstract
). Mutants showed a higher abundance of transcripts from mitochondrial genes encoding oxidative phosphorylation protein complexes, whereas nuclear genes encoding other subunits of the same complexes showed no change in transcript abundance. By contrast, the protein abundance of specific nuclear-encoded subunits in oxidative phosphorylation complexes I and V increased in CLPP2 knockouts, without accumulation of mitochondrial-encoded counterparts in the same complex. Complexes with subunits mainly or entirely encoded in the nucleus were unaffected. Analysis of protein import and function of complex I revealed that while function was retained, protein homeostasis was disrupted, leading to accumulation of soluble subcomplexes of nuclear-encoded subunits. Therefore, CLPP2 contributes to the mitochondrial protein degradation network through supporting coordination and homeostasis of protein complexes encoded across mitochondrial and nuclear genomes.