Calcium signaling pathways regulate mitochondrial morphology

Abstract

Mitochondria play extensive roles in cells by performing dynamic movement and morphological changes. Mitochondria maintain the elongated morphology and appropriate volume by the balance of fusion and division. However, it is unclear how mitochondria perform morphological changes in response to the external stimulation. We have investigated the intracellular signaling pathways that regulate the mitochondrial morphology in cultured hippocampal neurons. Mitochondria were labeled by expressing mitochondria-targeted fluorescent protein and their movement and morphology were monitored with real time imaging. High potassium stimulation induced a division-like changes and cessation of movement. This effect was dependent on the activation of N and P/Q types of voltage-dependent Ca²⁺channel (VDCC). A Ca²⁺/Calmodulin-dependent kinase inhibitor, KN93 blocked this change, but KN92 had no effect. Expression of dominant negative CaMKI blocked the mitochondrial response to potassium stimulation. On the other hand, glutamate stimulation induced the slow onset of movement freezing and morphological contraction. These changes were dependent on the activation of NMDA receptors and calcineurin signaling pathway. These results demonstrated that mitochondrial dynamics and morphological changes are regulated by distinctive intracellular signaling pathways associated with specific calcium channels. [Jpn J Physiol 54 Suppl:S83 (2004)]