MFF SUMOylation regulates neuronal mitochondrial morphology and facilitates AMPK-induced mitochondrial fragmentation
- 1School of Psychology and Neuroscience, University of Bristol
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.
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BibTeX
@misc{seager2026sumoylation,
title = {{MFF SUMOylation regulates neuronal mitochondrial morphology and facilitates AMPK-induced mitochondrial fragmentation}},
author = {R. Seager and D. Franchini and J. Henley and K. Wilkinson},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.07.749864},
url = {https://www.biorxiv.org/content/10.64898/2026.09.07.749864v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - MFF SUMOylation regulates neuronal mitochondrial morphology and facilitates AMPK-induced mitochondrial fragmentation
AU - R. Seager
AU - D. Franchini
AU - J. Henley
AU - K. Wilkinson
PY - 2026
DA - 2026/09/07
PB - bioRxiv
DO - 10.64898/2026.09.07.749864
UR - https://www.biorxiv.org/content/10.64898/2026.09.07.749864v1
AB - 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.
ER -