Cell biology

Biology

Calcium

Signal transduction

Neurodegeneration

Biochemistry

Endoplasmic reticulum

Homeostasis

Organic chemistry

Oxidative phosphorylation

Internal medicine

Mitochondrion

Medicine

Chemistry

Calcium signaling

Disease

Calcium metabolism

Proceedings of the National Academy of Sciences

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.

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