1. Temporal Profiling of the Cortical Synaptic Mitochondrial Proteome Identifies Ageing Associated Regulators of Stability.
- Author
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Graham LC, Kline RA, Lamont DJ, Gillingwater TH, Mabbott NA, Skehel PA, and Wishart TM
- Subjects
- Animals, Brain metabolism, Brain pathology, Disease Models, Animal, Drosophila genetics, Drosophila physiology, Gene Expression Regulation genetics, Humans, Mice, Mitochondria genetics, Muscular Dystrophies pathology, Neuromuscular Junction genetics, Neuromuscular Junction pathology, Neurons metabolism, Aging genetics, Mitochondrial Proteins genetics, Muscular Dystrophies genetics, Proteome genetics, Synapses genetics
- Abstract
Synapses are particularly susceptible to the effects of advancing age, and mitochondria have long been implicated as organelles contributing to this compartmental vulnerability. Despite this, the mitochondrial molecular cascades promoting age-dependent synaptic demise remain to be elucidated. Here, we sought to examine how the synaptic mitochondrial proteome (including strongly mitochondrial associated proteins) was dynamically and temporally regulated throughout ageing to determine whether alterations in the expression of individual candidates can influence synaptic stability/morphology. Proteomic profiling of wild-type mouse cortical synaptic and non-synaptic mitochondria across the lifespan revealed significant age-dependent heterogeneity between mitochondrial subpopulations, with aged organelles exhibiting unique protein expression profiles. Recapitulation of aged synaptic mitochondrial protein expression at the Drosophila neuromuscular junction has the propensity to perturb the synaptic architecture, demonstrating that temporal regulation of the mitochondrial proteome may directly modulate the stability of the synapse in vivo.
- Published
- 2021
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