Clarification of mitochondrial malformation and ultrastructural change by new correlative light and electron microscopy

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K14744
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44040:Morphology and anatomical structure-related
• Research Institution: Kurume University
• Principal Investigator: Miyazono Yoshihiro 久留米大学, 医学部, 臨床研究員 (80748674)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ミトコンドリア / FIB/SEM / Live-imaging 3D CLEM

Outline of Final Research Achievements

Loss of mitochondrial membrane potential (ΔΨm) triggers dramatic structural changes in mitochondria from a tubular to globular shape, referred to as mitochondrial fragmentation; the resulting globular mitochondria are called swelled or ring/doughnut mitochondria. We evaluated structural changes during the ΔΨm loss-induced transformation after carbonyl cyanide m-chlorophenyl hydrazine (CCCP) and valinomycin administration using a newly developed correlative microscopic method combined with fluorescence microscopic live imaging and volume electron microscopy. We found that most mitochondria changed from a tubular shape to a globular shape without fusion or fission and typically showed ring shapes after CCCP and Varinomycin exposure. In contrast, most ring mitochondria did not have a true through hole; rather, they had various indents, Our results suggested that loss of ΔΨm triggered collapse of mitochondrial structural support mechanisms.

Free Research Field

ミトコンドリア

Academic Significance and Societal Importance of the Research Achievements

本研究では細胞内の膜電位低下ストレスに応じてミトコンドリアの形態がどのように変化するのかを形態的に明らかにすることを目的とした。ミトコンドリアは細胞内のストレスに対する適応反応としてリング状や顆粒状へと形態変化するが、ミトコンドリアの形態変化についての詳細は不明なままである。本研究では、細胞実験においてミトコンドリア形態変化の初動を動的かつ3次元的に捉えるため、形態異常のミトコンドリアを誘導後、電子顕微鏡FIB/SEMと光学顕微鏡を組み合わせたライブイメージング・三次元光-電子相関顕微鏡法を用いた。その動的変化と超微細構造変化はミトコンドリア形態変化の基盤的知見になり得ると考える。