MFF SUMOylation regulates neuronal mitochondrial morphology and facilitates AMPK-induced mitochondrial fragmentation

Mitochondrial dysfunction and fragmentation are common features of many neurodegenerative diseases. AMP-activated protein kinase (AMPK), a cellular energy sensor, is often hyperactivated in Alzheimer's disease. When stressed, AMPK activates the phosphorylation of the outer mitochondrial membrane protein mitochondrial fission factor (MFF), resulting in SUMOylation at Lys151.

This MFF SUMOylation encourages fission, leading to mitochondrial fragmentation. Researchers conducted a study using primary neuronal culture to examine the role of MFF SUMOylation in mitochondrial morphology and function. They discovered that MFF SUMOylation is essential for maintaining the length of neuronal mitochondria under normal conditions in both axons and dendrites.

When AMPK is activated (using AICAR), preventing MFF SUMOylation reduces AICAR-induced fragmentation of dendritic mitochondria. This research clarifies that the AMPK-MFF-SUMO pathway is vital for neuronal mitochondrial fission.