Universität zu Köln

Hartmann, Bianca, Wai, Timothy ORCID: 0000-0002-6770-6222, Hu, Hao, MacVicar, Thomas, Musante, Luciana, Fischer-Zirnsak, Bjoern, Stenzel, Werner, Graef, Ralph, van den Heuvel, Lambert, Ropers, Hans-Hilger, Wienker, Thomas F., Huebner, Christoph, Langer, Thomas ORCID: 0000-0003-1250-1462 and Kaindl, Angela M. (2016). Homozygous YME1L1 Mutation Causes Mitochondriopathy with Optic Atrophy and Mitochondrial Network Fragmentation. eLife, 5. CAMBRIDGE: ELIFE SCIENCES PUBLICATIONS LTD. ISSN 2050-084X

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Abstract

Mitochondriopathies often present clinically as multisystemic disorders of primarily high-energy consuming organs. Assembly, turnover, and surveillance of mitochondrial proteins are essential for mitochondrial function and a key task of AAA family members of metalloproteases. We identified a homozygous mutation in the nuclear encoded mitochondrial escape 1-like 1 gene YME1L1, member of the AAA protease family, as a cause of a novel mitochondriopathy in a consanguineous pedigree of Saudi Arabian descent. The homozygous missense mutation, located in a highly conserved region in the mitochondrial pre-sequence, inhibits cleavage of YME1L1 by the mitochondrial processing peptidase, which culminates in the rapid degradation of YME1L1 precursor protein. Impaired YME1L1 function causes a proliferation defect and mitochondrial network fragmentation due to abnormal processing of OPA1. Our results identify mutations in YME1L1 as a cause of a mitochondriopathy with optic nerve atrophy highlighting the importance of YME1L1 for mitochondrial functionality in humans.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hartmann, Bianca UNSPECIFIED UNSPECIFIED UNSPECIFIED Wai, Timothy UNSPECIFIED orcid.org/0000-0002-6770-6222 UNSPECIFIED Hu, Hao UNSPECIFIED UNSPECIFIED UNSPECIFIED MacVicar, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Musante, Luciana UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer-Zirnsak, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED Stenzel, Werner UNSPECIFIED UNSPECIFIED UNSPECIFIED Graef, Ralph UNSPECIFIED UNSPECIFIED UNSPECIFIED van den Heuvel, Lambert UNSPECIFIED UNSPECIFIED UNSPECIFIED Ropers, Hans-Hilger UNSPECIFIED UNSPECIFIED UNSPECIFIED Wienker, Thomas F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Huebner, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Langer, Thomas UNSPECIFIED orcid.org/0000-0003-1250-1462 UNSPECIFIED Kaindl, Angela M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-266744
DOI:	10.7554/eLife.16078
Journal or Publication Title:	eLife
Volume:	5
Date:	2016
Publisher:	ELIFE SCIENCES PUBLICATIONS LTD
Place of Publication:	CAMBRIDGE
ISSN:	2050-084X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CYTOCHROME-C-OXIDASE; I-AAA PROTEASE; SPASTIC PARAPLEGIA; SACCHAROMYCES-CEREVISIAE; INTERMEMBRANE SPACE; FUNCTIONAL-ANALYSIS; LEIGH-SYNDROME; OPA1; OMA1; DEGRADATION Multiple languages Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26674