고려대학교 생명과학대학 생명과학부/ 대학원 분자생명과학과

Neurons are extremely polarized structures with long axons and dendrites, which require proper distribution of mitochondria and maintenance of mitochondrial dynamics for neuronal functions and survival. To deliver metabolic energy to synaptic terminals where energy demands are high, mitochondrial anterograde transport is needed, while mitochondrial retrograde transport is required to repair or remove damaged mitochondria in axons. Emerging evidence shows that neurodegenerative diseases such as Parkinson’s, Alzheimer’s, and Huntington’s diseases are associated with defects in mitochondrial transport or dynamics. While these neurodegenerative diseases result from different genetic mutations or arise sporadically, the function of the respective gene products may be involved in common pathways leading to altered mitochondrial transport of dynamics in neurons. However, molecular mechanisms that regulate mitochondrial transport in neurons are not well characterized. It is generally believed that mitochondrial transport in axons is passive, while no feedback input from the mitochondria is considered. In this view, mitochondrial transport is regulated mainly by extracellular signals that modulate cytoplasmic Ca2+ influx, which in turn controls mitochondrial transport machinery. In contrast, we recently discovered that intramitochondrialCa2+plays a critical role in mitochondrial transport in axons, suggesting that intrinsic signals inside of mitochondria may be actively involved in mitochondrial transport.