Universität zu Köln

Wang, Shuaiyu, Jacquemyn, Julie, Murru, Sara, Martinelli, Paola, Barth, Esther, Langer, Thomas, Niessen, Carien M. and Rugarli, Elena I. ORCID: 0000-0002-5782-1067 (2016). The Mitochondrial m-AAA Protease Prevents Demyelination and Hair Greying. PLoS Genet., 12 (12). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1553-7404

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Abstract

The m-AAA protease preserves proteostasis of the inner mitochondrial membrane. It ensures a functional respiratory chain, by controlling the turnover of respiratory complex subunits and allowing mitochondrial translation, but other functions in mitochondria are conceivable. Mutations in genes encoding subunits of the m-AAA protease have been linked to various neurodegenerative diseases in humans, such as hereditary spastic paraplegia and spinocerebellar ataxia. While essential functions of the m-AAA protease for neuronal survival have been established, its role in adult glial cells remains enigmatic. Here, we show that deletion of the highly expressed subunit AFG3L2 in mature mouse oligodendrocytes provokes early-on mitochondrial fragmentation and swelling, as previously shown in neurons, but causes only late-onset motor defects and myelin abnormalities. In contrast, total ablation of the m-AAA protease, by deleting both Afg3l2 and its paralogue Afg3l1, triggers progressive motor dysfunction and demyelination, owing to rapid oligodendrocyte cell death. Surprisingly, the mice showed premature hair greying, caused by progressive loss of melanoblasts that share a common developmental origin with Schwann cells and are targeted in our experiments. Thus, while both neurons and glial cells are dependant on the mAAA protease for survival in vivo, complete ablation of the complex is necessary to trigger death of oligodendrocytes, hinting to cell-autonomous thresholds of vulnerability to m-AAA protease deficiency.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wang, Shuaiyu UNSPECIFIED UNSPECIFIED UNSPECIFIED Jacquemyn, Julie UNSPECIFIED UNSPECIFIED UNSPECIFIED Murru, Sara UNSPECIFIED UNSPECIFIED UNSPECIFIED Martinelli, Paola UNSPECIFIED UNSPECIFIED UNSPECIFIED Barth, Esther UNSPECIFIED UNSPECIFIED UNSPECIFIED Langer, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Niessen, Carien M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rugarli, Elena I. UNSPECIFIED orcid.org/0000-0002-5782-1067 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-253759
DOI:	10.1371/journal.pgen.1006463
Journal or Publication Title:	PLoS Genet.
Volume:	12
Number:	12
Date:	2016
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1553-7404
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HEREDITARY SPASTIC PARAPLEGIA; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; OXIDATIVE STRESS; AFG3L2; OLIGODENDROCYTES; REMYELINATION; DEGENERATION; CELLS; MICE Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25375