A5058393129- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Autophagy in Disease and Therapy
- Amyotrophic Lateral Sclerosis Research
- Metabolism and Genetic Disorders
- Psychosomatic Disorders and Their Treatments
- Neurogenetic and Muscular Disorders Research
- Sympathectomy and Hyperhidrosis Treatments
- Machine Learning in Bioinformatics
- Parkinson's Disease Mechanisms and Treatments
- Endoplasmic Reticulum Stress and Disease
- Cancer, Hypoxia, and Metabolism
- Enzyme Structure and Function
- RNA modifications and cancer
- Adipose Tissue and Metabolism
- Migraine and Headache Studies
- Expert finding and Q&A systems
- Protein Structure and Dynamics
- Ubiquitin and proteasome pathways
- Muscle Physiology and Disorders
National Institute of Neurological Disorders and Stroke
2020-2024
National Institutes of Health
2020-2024
University of Cambridge
2023
MRC Mitochondrial Biology Unit
2023
Medical Research Council
2023
University of Chicago
2020
University of Michigan–Ann Arbor
2016
Mitochondrial stress triggers a response in the cell’s mitochondria and nucleus, but how these responses are coordinated vivo is poorly understood. Here, we characterize family with myopathy caused by dominant p.G58R mutation mitochondrial protein CHCHD10. To understand disease etiology, developed knockin (KI) mouse model found that mutant CHCHD10 aggregated affected tissues, applying toxic to inner membrane. Unexpectedly, survival of CHCHD10-KI mice depended on protective mediated...
Abstract Dominant mutations in the mitochondrial paralogs coiled-helix-coiled-helix (CHCHD) domain 2 (C2) and CHCHD10 (C10) were recently identified as causing Parkinson’s disease amyotrophic lateral sclerosis/frontotemporal dementia/myopathy, respectively. The mechanism by which they disrupt cristae, however, has been uncertain. Using first C2/C10 double knockout (DKO) mice, we report that C10 pathogenesis normal function of are intimately linked. Similar to patients with mutations, found...
PINK1 and PRKN, which cause Parkinson disease when mutated, form a quality control mitophagy pathway that is well-characterized in cultured cells. The extent to the PINK1-PRKN contributes vivo, however, controversial. This due large part conflicting results from studies using one of two reporters: mt-Keima or mito-QC. Studies have generally detected whereas those mito-QC not. Here, we directly compared performance cell culture mice subjected activating stress. We found was less sensitive...
Abstract Mitochondrial dysfunction causes devastating disorders, including mitochondrial myopathy. Here, we identified that diverse myopathy models elicit a protective integrated stress response (mt-ISR), mediated by OMA1-DELE1 signaling. The was similar following disruptions in mtDNA maintenance, from knockout of Tfam , and protein unfolding, disease-causing mutations CHCHD10 (G58R S59L). preponderance the directed at upregulating pathways for aminoacyl-tRNA biosynthesis, intermediates...
Abstract Mutations affecting the mitochondrial intermembrane space protein CHCHD10 cause human disease, but it is not known why different amino acid substitutions markedly clinical phenotypes, including amyotrophic lateral sclerosis-frontotemporal dementia, spinal muscular atrophy Jokela-type, isolated autosomal dominant myopathy and cardiomyopathy. mutations have been associated with deletions of DNA (mtDNA deletions), raising possibility that these explain variability. Here, we sequenced...
Abstract Mitochondrial stress triggers a response in the cell’s mitochondria and nucleus, but how these responses are coordinated vivo is poorly understood. Here, we characterize family with myopathy caused by dominant p.G58R mutation mitochondrial protein CHCHD10. To understand disease etiology, developed novel knock-in mouse model found that mutant CHCHD10 aggregates affected tissues, applying toxic to inner membrane. Unexpectedly, survival of mice depended on protective mediated OMA1. The...