TY  - JOUR
A1  - Hartmann, Bianca
A1  - Wai, Timothy
A1  - Hu, Hao
A1  - MacVicar, Thomas
A1  - Musante, Luciana
A1  - Fischer-Zirnsak, Björn
A1  - Stenzel, Werner
A1  - Gräf, Ralph
A1  - van den Heuvel, Lambert
A1  - Ropers, Hans-Hilger
A1  - Wienker, Thomas F.
A1  - Hübner, Christoph
A1  - Langer, Thomas
A1  - Kaindl, Angela M.
T1  - Homozygous YME1L1 Mutation Causes Mitochondriopathy with Optic Atrophy and Mitochondrial Network Fragmentation
T2  - eLife
N2  - 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.
KW  - YME1L1
KW  - mitochondriopathy
KW  - intellectual disability
KW  - optic atrophy
KW  - OPA1
KW  - mitochondrial fragmentation
Y1  - 2016
UR  - https://publishup.uni-potsdam.de/frontdoor/index/index/docId/45064
SN  - 2050-084X
VL  - 5
SP  - 1156
EP  - 1165
PB  - eLife Sciences Publications
CY  - Cambridge
ER  -