Elucidation of molecular mechanisms and development of surrogate markers for multiple system atrophy caused by COQ2 mutations

2016 Fiscal Year Final Research Report

• Project/Area Number: 26253054
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: The University of Tokyo
• Principal Investigator: Tsuji Shoji 東京大学, 医学部附属病院, 教授 (70150612)
• Co-Investigator(Kenkyū-buntansha): 三井 純 東京大学, 医学部附属病院, 助教 (70579862)
• Co-Investigator(Renkei-kenkyūsha): GOTO Jun 東京大学, 医学部附属病院, 准教授 (10211252) ; MITSUI Jun 東京大学, 医学部附属病院, 助教 (70579862)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 多系統萎縮症 / COQ2 / フラックスアナライザー / coenzyme Q10 / ミトコンドリア

Outline of Final Research Achievements

In our previous studies, we found that COQ2 mutations are associated with familial as well as sporadic multiple system atrophy (MSA). To quantitatively evaluate the altered functions of COQ2 coding for an enzyme in the biosynthesis of CoQ10, we measured oxygen consumption rates (OCR) of yeast harboring mutant human COQ2 cDNA employing a Flux Analyzer. We prepared mutant yeast with a deletion of yeast COQ2 gene. We then transformed the yeast with mutant human COQ2 cDNA, and measured the OCRs of these yeast strains. We demonstrated that OCRs of yeast harboring V393A, a susceptibility variant for sporadic MSA, or M128V, a causative mutation for familial MSA, are significantly decreased. The results suggest that OCR measurement may be utilized as a surrogate marker for MSA.

Free Research Field

神経内科学，分子遺伝学