Dataset Information

Salvage pathway maintains functional respiratory complex I

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 steps in recent years. Although some studies indicated that CI might be remodelled in response to various stimuli, the mechanism mediating these putative changes is unknown. Here, we report that the NADH-oxidising N-module which sits on the tip of the CI peripheral arm is turned over at a higher rate and largely independently of the rest of the complex. The N-module turnover is mediated by mitochondrial matrix protease ClpXP, which selectively removes and degrades damaged core subunits. The observed mechanism seems to be a safeguard against accumulation of dysfunctional CI arising from inactivation of the N-module subunits due to attrition caused by extensive redox activity. This CI salvage pathway maintains highly functional CI and healthy mitochondria through an energetically favourable mechanism that demands much lower energetic cost than de novo synthesis and reassembly of the entire CI.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart, Cell Culture, Fibroblast

SUBMITTER: Karolina Szczepanowska

LAB HEAD: Aleksandra Trifunovic

PROVIDER: PXD014897 | Pride | 2020-03-05

REPOSITORIES: Pride

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			Action	DRS
	20161125_UC_ColID_251_KarolinaSzczepanowska_Trifunovic_ProjID_277_KO1_1.raw	Raw
	20161125_UC_ColID_251_KarolinaSzczepanowska_Trifunovic_ProjID_277_KO1_2.raw	Raw
	20161125_UC_ColID_251_KarolinaSzczepanowska_Trifunovic_ProjID_277_KO1_3.raw	Raw
	20161125_UC_ColID_251_KarolinaSzczepanowska_Trifunovic_ProjID_277_KO1_4.raw	Raw
	20161125_UC_ColID_251_KarolinaSzczepanowska_Trifunovic_ProjID_277_KO1_5.raw	Raw

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A salvage pathway maintains highly functional respiratory complex I.

Szczepanowska Karolina K Senft Katharina K Heidler Juliana J Herholz Marija M Kukat Alexandra A Höhne Michaela Nicole MN Hofsetz Eduard E Becker Christina C Kaspar Sophie S Giese Heiko H Zwicker Klaus K Guerrero-Castillo Sergio S Baumann Linda L Kauppila Johanna J Rumyantseva Anastasia A Müller Stefan S Frese Christian K CK Brandt Ulrich U Riemer Jan J Wittig Ilka I Trifunovic Aleksandra A

Nature communications 20200402 1

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 ...[more]

PMID: 32242014

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