Muscle choline kinase beta defect causes mitochondrial dysfunction and increased mitophagy

• DOI: 10.1093/hmg/ddr305
• Publication Date: 2011-07-13T12:04:21Z
• Authors: Satomi Mitsuhashi; Hideyuki Hatakeyama; Minako Karahashi; Tomoko Koumura; Ikuya Nonaka; Yukiko K. Hayashi; Satoru Noguchi; Roger B. Sher; Yasuhito Nakagawa; Giovanni Manfredi; Yu-ichi Goto; Gregory A. Cox; Ichizo Nishino
• Keywords: PINK1

Choline kinase is the first step enzyme for phosphatidylcholine (PC) de novo biosynthesis. Loss of choline activity in muscle causes rostrocaudal muscular dystrophy (rmd) mouse and congenital human, characterized by distinct mitochondrial morphological abnormalities. We performed biochemical pathological analyses on skeletal mitochondria from rmd mice. No were found center fibers, while those located at periphery fibers significantly enlarged. Muscle mice exhibited decreased PC levels, impaired respiratory chain activities, ATP synthesis, coenzyme Q increased superoxide production. Electron microscopy showed selective autophagic elimination muscle. Molecular markers mitophagy, including Parkin, PINK1, LC3, polyubiquitin p62, localized to Quantitative analysis shows that number DNA copy decreased. demonstrated genetic defect results dysfunction subsequent loss through enhanced activation mitophagy. These findings provide a evidence pathomechanistic link between biosynthesis abnormality.