06/11/2024 13:00
Sijie Li

Title: Mitochondria dynamic and its translocation during cellular stress conditions

 

Abstract

Mitochondria dynamics, motility, and translocation to distinct cellular regions by cytoskeleton-based machinery are essential for adapting to eukaryote cells’ physiological demands. Within this broad mitochondrial motility machinery, the specialized function of actin-based motors has begun to emerge. Precisely, it is not understood how mitochondrial motility is coordinated and regulated and how it is coupled to cellular processes to perform its functions. Using interdisciplinary approaches, we show that mitochondria mobility to the cell’s leading edge upon EGF stimulation is manifested by a fission event that enables mitochondria to reach filopodia in A431. Mitochondria translocation to the leading edge and filopodia required MT-and actin-based motors, Kif5b and Myo19, respectively, and critically, their cooperativity. Importantly, we have found that local calcium buffering affects Kif5b-mitochondria association but has no significant impact on Myo19-mitochondria association both in-vivo and in-vitro. Hence, we suggest a switch-over mechanism between MT- and actin-based motors in cargo transport in-cells such as mitochondria. Our finding supports coordination for mitochondria motility that requires bridging between actin and MT-base motors. Mitochondria dynamics, motility, and cell positioning are essential in development and homeostasis. Failure to regulate these processes directly leads to broad pathogenesis and many cell types. A comprehensive mechanism to describe the complete processes is still at large. My PhD thesis dissertation shed light on such biochemical pathways.