Altered ER–mitochondria contact impacts mitochondria calcium homeostasis and contributes to neurodegeneration in vivo in disease models

作者：Kyu‐Sun Lee, Sungun Huh, Seongsoo Lee, Zhihao Wu, Ae‐Kyeong Kim, Ha‐Young Kang, Bingwei Lu · 发表于：Proceedings of the National Academy of Sciences · 年份：2018 · DOI：10.1073/pnas.1721136115 · 被引用次数：245 · 研究领域：Mitochondrial Function and Pathology、Genetic Neurodegenerative Diseases、Endoplasmic Reticulum Stress and Disease

Significance Ca 2 + regulates cellular metabolism, proliferation, and differentiation. Ca 2+ homeostasis is critical for cellular function and health. Mitochondria help buffer transient Ca 2+ elevations and prevent cell death induced by Ca 2+ overload. Mito-Ca 2+ is also required for optimal activity of certain key mitochondrial functions, such as oxidative phosphorylation and metabolism. Thus, mito-Ca 2+ homeostasis assumes central roles in cellular health. Endoplasmic reticulum (ER) and mitochondria make intimate contacts and exchange molecules such as Ca 2+ and lipids. We find that ER-to-mitochondria Ca 2+ transfer is important for mito-Ca 2+ homeostasis and that the conserved Miro protein is critically involved. We show that mito-Ca 2+ homeostasis is disrupted in neurodegenerative disease models and its restoration is beneficial. Our findings have important implications for therapeutic intervention of neurodegenerative diseases.