title: Mitochondrial CHCHD-Containing Proteins: Physiologic Functions and Link with Neurodegenerative Diseases.
abstract: The coiled-coil-helix-coiled-coil-helix domain (CHCHD)-containing proteins are evolutionarily conserved nucleus-encoded small mitochondrial proteins with important functions. So far, nine members have been identified in this protein family. All CHCHD proteins have at least one functional coiled-coil-helix-coiled-coil-helix (CHCH) domain, which is stabilized by two pairs of disulfide bonds between two helices. CHCHD proteins have various important pathophysiological roles in mitochondria and other key cellular processes. Mutations of CHCHD proteins have been associated with various human neurodegenerative diseases. Mutations of CHCHD10 are associated with amyotrophic lateral sclerosis (ALS) and/or frontotemporal lobe dementia (FTD), motor neuron disease, and late-onset spinal muscular atrophy and autosomal dominant mitochondrial myopathy. CHCHD10 stabilizes mitochondrial crista ultrastructure and maintains its integrity. In patients with CHCHD10 mutations, there are abnormal mitochondrial crista structure, deficiencies of respiratory chain complexes, impaired mitochondrial respiration, and multiple mitochondrial DNA (mtDNA) deletions. Recently, CHCHD2 mutations are linked with autosomal dominant and sporadic Parkinson's disease (PD). The CHCHD2 is a multifunctional protein and plays roles in regulation of mitochondrial metabolism, synthesis of respiratory chain components, and modulation of cell apoptosis. With a better understanding of the pathophysiologic roles of CHCHD proteins, they may be potential novel therapeutic targets for human neurodegenerative diseases.
authors.affiliation: National Neuroscience Institute of Singapore, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore. Zhidong_zhou@nni.com.sg.|Signature Research Program in Neuroscience and Behavioural Disorders, Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore, 169857, Singapore. Zhidong_zhou@nni.com.sg.
authors.forename: Zhi-Dong
authors.initials: ZD
authors.lastname: Zhou
authors.affiliation: National Neuroscience Institute of Singapore, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore.
authors.forename: Wuan-Ting
authors.initials: WT
authors.lastname: Saw
authors.affiliation: National Neuroscience Institute of Singapore, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore. Tan.eng.king@sgh.com.sg.|Signature Research Program in Neuroscience and Behavioural Disorders, Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore, 169857, Singapore. Tan.eng.king@sgh.com.sg.|Department of Neurology, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore. Tan.eng.king@sgh.com.sg.
authors.forename: Eng-King
authors.initials: EK
authors.lastname: Tan
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins
keywords: Apoptosis; Coiled-coil-helix-coiled-coil-helix domain proteins; Mitochondria; Mitochondrial cristae; Neurodegenerative disease