INTRODUCTION: Neuronal cells depend on mitochondrial activity to maintain membrane excitability, neurotransmission, and synaptic plasticity. The AMP-activated protein kinase (AMPK) signalling pathway plays a crucial role in regulating cellular energy homeostasis and has been found to influence mitochondrial dynamics. The dynamics of these organelles determine their morphology, allowing them to adapt to metabolic requirements. Furthermore, the phosphorylation of DRP1, the major protein involved in mitochondrial fission/fusion, is essential for controlling mitochondrial dynamics, synapse maturation, synaptic transmission and plasticity. A mutation (p.Q639*) in the TRAP1 gene, which encodes the mitochondrial chaperone, was identified in an ASD patient, their monozygotic twin brother was unaffected. TRAP1 belongs to the HSP-90 family of proteins, which are involved in protecting against oxidative stress and regulating the metabolism of cells. Indeed, many neurodevelopmental disorders have been observed to be linked to mitochondrial dysfunction.

AIM(S): We investigated mitochondrial dynamics and AMPK signalling in the hippocampi of Trap1 mice

METHOD(S): Mitochondria from the hippocampi of Trap1 mutant and WT mice were isolated, and the levels and phosphorylation of proteins involved in fission and fusion were assessed in both sexes. Also, AMPK signalling was analysed, which is connected with the regulation of mitochondrial dynamics.

RESULTS: We observe sex-specific alterations in mitochondrial dynamics in the hippocampus.

CONCLUSIONS: In Trap1 mutant mice, there is a change in fission-fusion proteins level and their activity in mitochondria isolated from the hippocampus. Also, we observe differences in the regulation of mitochondrial dynamics between sexes

FINANCIAL SUPPORT: This work was supported by the National Science Centre, Poland under research projects: OPUS 2019/35/b/NZ4/04355 and OPUS 2023/51/B/NZ4/00856