The role of deleted-mtDNA accumulation in the molecular mechanism underlying the pathogenesis of mood disorders

• Project/Area Number: 25891032
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Cell biology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: SAWADA Tomoyo 独立行政法人理化学研究所, 脳科学総合研究センター, 研究員 (90708471)
• Project Period (FY): 2013-08-30 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: mtDNA / 双極性障害

Outline of Final Research Achievements

Clonal accumulation of deleted-mtDNA caused by POLG1 mutation in the specific neural circuit is thought to be one of the molecular mechanisms underlying the pathogenesis of mood disorders. To analyze the neuronal dysfunction caused by the accumulation of deleted-mtDNA, we established a method for the quantification of deleted-mtDNA in cells dissected from mouse brain by qPCR. We also generated induced-pluripotent stem (iPS) cells from human peripheral blood mononuclear cells using episomal vectors, and successfully differentiated them into neurons, to generate PLOG1 mutant iPS cells using genome editing methods.