A heteroplasmic mitochondrial complex I gene mutation in adult-onset dystonia

Neurogenetics ◽  
2003 ◽  
Vol 4 (4) ◽  
pp. 199-205 ◽  
Author(s):  
DavidK. Simon ◽  
Jennifer Friedman ◽  
XandraO. Breakefield ◽  
Joseph Jankovic ◽  
MitchellF. Brin ◽  
...  
2001 ◽  
Vol 38 (1) ◽  
pp. 58-61 ◽  
Author(s):  
D. K. SIMON ◽  
M. A. TARNOPOLSKY ◽  
J. T. GREENAMYRE ◽  
D. R. JOHNS

2019 ◽  
Vol 18 (8) ◽  
pp. e3041
Author(s):  
B. Schöpf ◽  
H. Weissensteiner ◽  
G. Schäfer ◽  
A. Naschberger ◽  
B. Rupp ◽  
...  

Genes ◽  
2019 ◽  
Vol 10 (7) ◽  
pp. 532
Author(s):  
Misa Hirose ◽  
Paul Schilf ◽  
Kim Zarse ◽  
Hauke Busch ◽  
Georg Fuellen ◽  
...  

Mitochondrial complex I—the largest enzyme complex of the mitochondrial oxidative phosphorylation machinery—has been proposed to contribute to a variety of age-related pathological alterations as well as longevity. The enzyme complex-consisting proteins are encoded by both nuclear (nDNA) and mitochondrial DNA (mtDNA). While some association studies of mtDNA encoded complex I genes and lifespan in humans have been reported, experimental evidence and the functional consequence of such variants is limited to studies using invertebrate models. Here, we present experimental evidence that a homoplasmic mutation in the mitochondrially encoded complex I gene mt-Nd2 modulates lifespan by altering cellular tryptophan levels and, consequently, ageing-related pathways in mice. A conplastic mouse strain carrying a mutation at m.4738C > A in mt-Nd2 lived slightly, but significantly, shorter than the controls did. The same mutation led to a higher susceptibility to glucose intolerance induced by high-fat diet feeding. These phenotypes were not observed in mice carrying a mutation in another mtDNA encoded complex I gene, mt-Nd5, suggesting the functional relevance of particular mutations in complex I to ageing and age-related diseases.


2018 ◽  
Author(s):  
Misa Hirose ◽  
Paul Schilf ◽  
Kim Zarse ◽  
Hauke Busch ◽  
Georg Füllen ◽  
...  

AbstractMitochondrial complex I, the largest enzyme complex of the mitochondrial oxidative phosphorylation machinery, has been proposed to contribute to a variety of age-related pathological alterations as well as longevity. The enzyme complex-consisting proteins are encoded by both nuclear (nDNA) and mitochondrial DNA (mtDNA). While some association studies of mtDNA-encoded complex I genes and lifespan in humans have been reported, experimental evidence and the functional consequence of such variants is limited to studies using invertebrate models. Here, we present experimental evidence that a homoplasmic mutation in the mitochondrially encoded complex I gene mt-Nd2 modulates lifespan by altering cellular tryptophan levels and, consequently, ageing-related pathways in mice. A conplastic mouse strain carrying a mutation at m.4738C>A in mt-Nd2 lived significantly shorter than the controls did. The same mutation led to a higher susceptibility to glucose intolerance induced by high-fat diet feeding. These phenotypes were not observed in mice carrying a mutation in another mtDNA-encoded complex I gene, mt-Nd5, suggesting the functional relevance of particular mutations in complex I to ageing and age-related diseases.


2014 ◽  
Vol 345 (1-2) ◽  
pp. 220-223 ◽  
Author(s):  
Ahmad Poursadegh Zonouzi ◽  
Saeid Ghorbian ◽  
Morteza Abkar ◽  
Ali Akbar Poursadegh Zonouzi ◽  
Ali Azadi

2007 ◽  
Vol 64 (7) ◽  
pp. 1042 ◽  
Author(s):  
David K. Simon ◽  
Kangni Zheng ◽  
Luis Velázquez ◽  
Nieves Santos ◽  
Luis Almaguer ◽  
...  

2006 ◽  
Vol 2006 ◽  
pp. 1-8 ◽  
Author(s):  
Elizabeth H. Corder ◽  
George D. Mellick

Parkinson's disease (PD) is a common age-related neurodegenerative disorder thought to result from the integrated effects of genetic background and exposure to neuronal toxins. Certain individual nuclear-encoded mitochondrial complex I gene polymorphisms were found to be associated with∼2-fold risk variation in an Australian case-control sample. We further characterized this sample of306cases and321controls to determine the mutual information contained in the22SNPs and, additionally, level of pesticide exposure: five distinct risk sets were identified using grade-of-membership analysis. Of these, one was robust to pesticide exposure (I), three were vulnerable (II, III, IV), and another (V) denoted low risk for unexposed persons. Risk for individual subjects varied>16-fold according to level of membership in the vulnerable groups. We conclude that inherited variation in mitochondrial complex I genes and pesticide exposure together modulate risk for PD.


Sign in / Sign up

Export Citation Format

Share Document