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

Authors

Seager, R., Franchini, D., Henley, J., Wilkinson, K.

Abstract

Mitochondrial dysfunction and fragmentation in neurons are characteristics of many neurodegenerative conditions. AMP-activated protein kinase (AMPK) is a cellular energy sensor which is hyperactivated in Alzheimers disease. Under stress conditions, AMPK-mediates phosphorylation of the outer mitochondrial membrane protein mitochondrial fission factor (MFF), leading to SUMOylation at Lys151. MFF SUMOylation promotes fission and subsequent mitochondrial fragmentation. Here, using primary neuronal culture, we investigate the role of MFF SUMOylation in mitochondrial morphology and function. We show that MFF SUMOylation is required to maintain neuronal mitochondrial length under basal conditions in axons and dendrites. Using the AMPK activator (AICAR) to induce mitochondrial fission, show that preventing MFF SUMOylation reduces AICAR-induced fragmentation of dendritic mitochondria. These findings reconcile observations of AMPK hyperactivation and mitochondrial fragmentation by revealing the AMPK-MFF-SUMO pathway to be crucial in neuronal mitochondrial fission.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 12 Sep 2026.

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