title: A peep into mitochondrial disorder: multifaceted from mitochondrial DNA mutations to nuclear gene modulation.
abstract: Mitochondrial genome is responsible for multiple human diseases in a maternal inherited pattern, yet phenotypes of patients in a same pedigree frequently vary largely. Genes involving in epigenetic modification, RNA processing, and other biological pathways, rather than "threshold effect" and environmental factors, provide more specific explanation to the aberrant phenotype. Thus, the double hit theory, mutations both in mitochondrial DNA and modifying genes aggravating the symptom, throws new light on mitochondrial dysfunction processes. In addition, mitochondrial retrograde signaling pathway that leads to reconfiguration of cell metabolism to adapt defects in mitochondria may as well play an active role. Here we review selected examples of modifier genes and mitochondrial retrograde signaling in mitochondrial disorders, which refine our understanding and will guide the rational design of clinical therapies.
authors.affiliation: School of Medicine, Institute of Genetics, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: School of Medicine, Institute of Genetics, Zhejiang University, Hangzhou, 310058, China. yechency@zju.edu.cn.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, 310058, China. yechency@zju.edu.cn.
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Medicine, Institute of Genetics, Zhejiang University, Hangzhou, 310058, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Min-Xin
authors.initials: MX
authors.lastname: Guan
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D015398:Signal Transduction
chemical_list: D004272:DNA, Mitochondrial
keywords: mitochondrial DNA mutation; mitochondrial disorder; mitochondrial retrograde signaling; nuclear modifier gene