Abstract 13568: Proteomic Analysis Reveals Protein Alterations in Drp1 Cardiac Knockout Mice With Circadian Rhythm Disruption

Introduction: Mitochondria dynamics are altered in circadian rhythm disruption, and dynamin-related protein 1 (Drp1) may be an important target.

Methods: Wild-type and Drp1 cardiac-specific knockout mice were divided into normal circadian group and circadian disorder group, respectively. Normal circadian group mice were housed in a standard environment (12 hours of light/12 hours of darkness), while dark group mice were housed in a 24-hour dark environment. After 4 weeks, the cardiac tissues were analysed using Tandem Mass Tag proteomics. Differentially expressed proteins (DEPs) was identified. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Gene set enrichment analysis (GSEA) was performed to find enriched biological processes.

Results: Compared with the WT/N group, the Drp1-/N group possessed a total of 176 DEPs. These proteins are widely involved in mitochondrial membrane and metabolism process. We identified several differentially expressed mitochondrial dynamics-related genes, including Drp1, using Western blotting. Compared with the WT/D group, the Drp1-/D group exhibited a total of 126 DEPs. GO and KEGG showed that the DEPs were mainly involved in response to stress, metabolic pathways. For Drp1 cKO mice, the protein changes caused by the circadian rhythm disorder were mainly concentrated in vitamin transport, complement coagulation cascades.

Conclusions: This study may provide an insight into the myocardial protein changes caused by Drp1 cKO with circadian rhythm disruption, which may involve in terms such as metabolic pathways, complement coagulation, and vitamin transport.