Temporal Profiling of the Cortical Synaptic Mitochondrial Proteome Identifies Ageing Associated Regulators of Stability

Cells

卷:10

Thomas H. Gillingwater¹  Paul A. Skehel¹  Douglas J. Lamont²  Laura C. Graham³  Rachel A. Kline³  Thomas M. Wishart³  Neil A. Mabbott³ 

[1] Euan MacDonald Centre, Chancellor’s Building, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK;

[2] FingerPrints Proteomic Facility, College of Life Sciences, University of Dundee, Dow Street DD1 5EH, UK;

[3] The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK;

关键词: mitochondria;    synapse;    aging;    proteomics;    neuron;   

DOI  :  10.3390/cells10123403

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown