Szczepanowska 2020 Nat Commun

From Bioblast
Jump to: navigation, search
Publications in the MiPMap
Szczepanowska K, Senft K, Heidler J, Herholz M, Kukat A, Höhne MN, Hofsetz E, Becker C, Kaspar S, Giese H, Zwicker K, Guerrero-Castillo S, Baumann L, Kauppila J, Rumyantseva A, Müller S, Frese CK, Brandt U, Riemer J, Wittig I, Trifunovic A (2020) A salvage pathway maintains highly functional respiratory complex I. Nat Commun 11:1643.

» PMID: 32242014 Open Access

Szczepanowska K, Senft K, Heidler J, Herholz M, Kukat A, Hoehne MN, Hofsetz E, Becker C, Kaspar S, Giese H, Zwicker K, Guerrero-Castillo S, Baumann L, Kauppila J, Rumyantseva A, Mueller S, Frese CK, Brandt U, Riemer J, Wittig I, Trifunovic A (2020) Nat Commun

Abstract: Regulation of the turnover of complex I (CI), the largest mitochondrial respiratory chain complex, remains enigmatic despite huge advancement in understanding its structure and the assembly. Here, we report that the NADH-oxidizing N-module of CI is turned over at a higher rate and largely independently of the rest of the complex by mitochondrial matrix protease ClpXP, which selectively removes and degrades damaged subunits. The observed mechanism seems to be a safeguard against the accumulation of dysfunctional CI arising from the inactivation of the N-module subunits due to attrition caused by its constant activity under physiological conditions. This CI salvage pathway maintains highly functional CI through a favorable mechanism that demands much lower energetic cost than de novo synthesis and reassembly of the entire CI. Our results also identify ClpXP activity as an unforeseen target for therapeutic interventions in the large group of mitochondrial diseases characterized by the CI instability.


Bioblast editor: Plangger M O2k-Network Lab: DE Cologne Trifunovic A, DE Frankfurt Wittig I, NL Nijmegen Brandt U


Labels: MiParea: Respiration, mt-Structure;fission;fusion, mtDNA;mt-genetics 


Organism: Caenorhabditis elegans 


Enzyme: Complex I 


HRR: Oxygraph-2k 

2020-04