Mitochondrial brain proteome acetylation levels and behavioural responsiveness to amphetamine are altered in mice lacking Sirt3

• DOI: 10.3389/fphys.2022.948387
• Publication Date: 2022-09-06T10:19:57Z
• Authors: Elena Sidorova-Da...; Merrick S. Fallah; Richard Logan; Cheng Yu Lin; James H. Eubanks
• Keywords: SIRT3; Proteome

Post-translational modification of mitochondrial proteins represents one mechanism by which the functional activity mitochondria can be regulated. In brain, these modifications influence properties different neural circuitries. Given that sirtuin family member Sirt3 primary protein deacetylase enzyme in mitochondria, we tested whether brain proteome acetylation would increase male or female mice lacking Sirt3. Our results confirm whole levels are indeed elevated both sexes Sirt3-KO relative to controls. Consistently, found mouse embryonic fibroblast (MEF) cells derived from were smaller size, and fewer number than wild-type MEFs, free calcium within cells. As function, changes function have been linked alterations circuit regulating motor anxiety-like behavior, Sirt3-deficient display sensitized responsiveness stimulant amphetamine. Both Sirt 3 -KO displayed hyper-locomotion attenuated behavior response a dose amphetamine was insufficient promote any behavioural responses mice. Collectively, regulates tissue, absence increases sensitivity systems amphetamine-induced responses.