Universität zu Köln

Szczepanowsk, Karolina, Senft, Katharina, Heidler, Juliana, Herholz, Marija, Kukat, Alexandra, Hoehne, Michaela Nicole, Hofsetz, Eduard ORCID: 0000-0001-5830-4566, Becker, Christina, Kaspar, Sophie ORCID: 0000-0002-0844-6432, Giese, Heiko, Zwicker, Klaus, Guerrero-Castillo, Sergio ORCID: 0000-0002-6630-0562, Baumann, Linda, Kauppila, Johanna, Rumyantseva, Anastasia, Mueller, Stefan, Frese, Christian K., Brandt, Ulrich ORCID: 0000-0003-1869-6811, Riemer, Jan, Wittig, Ilka and Trifunovic, Aleksandra (2020). A salvage pathway maintains highly functional respiratory complex I. Nat. Commun., 11 (1). LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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. Maintenance and quality control of the mitochondrial respiratory chain complexes responsible for bulk energy production are unclear. Here, the authors show that the mitochondrial protease ClpXP is required for the rapid turnover of the core N-module of respiratory complex I, which happens independently of other modules in the complex.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Szczepanowsk, Karolina UNSPECIFIED UNSPECIFIED UNSPECIFIED Senft, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Heidler, Juliana UNSPECIFIED UNSPECIFIED UNSPECIFIED Herholz, Marija UNSPECIFIED UNSPECIFIED UNSPECIFIED Kukat, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoehne, Michaela Nicole UNSPECIFIED UNSPECIFIED UNSPECIFIED Hofsetz, Eduard UNSPECIFIED orcid.org/0000-0001-5830-4566 UNSPECIFIED Becker, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaspar, Sophie UNSPECIFIED orcid.org/0000-0002-0844-6432 UNSPECIFIED Giese, Heiko UNSPECIFIED UNSPECIFIED UNSPECIFIED Zwicker, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Guerrero-Castillo, Sergio UNSPECIFIED orcid.org/0000-0002-6630-0562 UNSPECIFIED Baumann, Linda UNSPECIFIED UNSPECIFIED UNSPECIFIED Kauppila, Johanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Rumyantseva, Anastasia UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Frese, Christian K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brandt, Ulrich UNSPECIFIED orcid.org/0000-0003-1869-6811 UNSPECIFIED Riemer, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Wittig, Ilka UNSPECIFIED UNSPECIFIED UNSPECIFIED Trifunovic, Aleksandra UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-337691
DOI:	10.1038/s41467-020-15467-7
Journal or Publication Title:	Nat. Commun.
Volume:	11
Number:	1
Date:	2020
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-1723
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SUPEROXIDE GENERATION; CHAIN COMPLEXES; MITOCHONDRIA; SUBUNIT; MUTATIONS; STABILITY; NADH; ASSEMBLY/STABILITY; IDENTIFICATION; OXIDATION Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/33769