Abstract
The transitioning of cells during the systemic demise of an organism is poorly understood. Here, we present evidence that organismal death is accompanied by a common and sequential molecular flood of stress-induced events that propagate the senescence phenotype, and this phenotype is preserved in the proteome after death. We demonstrate activation of “death” pathways involvement in diseases of ageing, with biochemical mechanisms mapping onto neurological damage, embryonic development, the inflammatory response, cardiac disease and ultimately cancer with increased significance. There is sufficient bioavailability of the building blocks required to support the continued translation, energy, and functional catalytic activity of proteins. Significant abundance changes occur in 1258 proteins across 1 to 720 h post-mortem of the 12-week-old mouse mandible. Protein abundance increases concord with enzyme activity, while mitochondrial dysfunction is evident with metabolic reprogramming. This study reveals differences in protein abundances which are akin to states of stress-induced premature senescence (SIPS). The control of these pathways is significant for a large number of biological scenarios. Understanding how these pathways function during the process of cellular death holds promise in generating novel solutions capable of overcoming disease complications, maintaining organ transplant viability and could influence the findings of proteomics through “deep-time” of individuals with no historically recorded cause of death.
Highlights
The leading contributors to death for older Australians are vascular and coronary heart disease, dementia related disorders, infection and immunological complications [1]; common causes to the decline in health echoed around the world
The database (Spectral count through Post-Mortem Time.xls) has the option to filter for specific protein properties allowing the tracking of proteins relevant in other contexts such as disease, ageing and paleoproteomics
Collagen is a common protein within mouse dentaries that does not undergo degradation in the time scales assayed [29], it can be used as a sampling control
Summary
The leading contributors to death for older Australians are vascular and coronary heart disease, dementia related disorders, infection and immunological complications [1]; common causes to the decline in health echoed around the world. Sci. 2020, 21, 6422 regulation in response to stress in a GTP dependent manner; a scenario which is mimicked in the PM transcriptome [13] These processes are heavily regulated by phosphorylation within the protein complex and translational repression of most mRNA with a selective upregulation of around 2.5% of total mRNAs [23]. The 2nd major process for energy production, called oxidative phosphorylation, involves the electron transport chain within the inner membrane of a mitochondrion It involves the transfer of electrons from NADH and FADH2 through several protein complexes and to oxygen to form water [25]. This study goes beyond the limits of survival to demonstrate that the machinery for survival persists and continues to function
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