Ανάλυση της λειτουργικής συμμετοχής ρυθμιστών της ομοιοστασίας των μιτοχονδρίων στη γήρανση και τις νόσους του γήρατος ; Analysis of the functional involvement of mitochondrial homeostasis regulators in aging and age-related diseases

The survival of organisms depends on the ability to regulate their metabolism to produce energy and regulate cellular responses to stressors to maintain the integrity and functionality of their biomolecules (eg, genome, proteome). At the organismal level, these responses require overly complex, still largely unknown, interconnections and inter-regulations of cell-autonomous and non-autonomous mechanisms. In this setting, mitochondria have critical anabolic and catabolic functions to metabolize nutrients and adjust cellular physiology through the operation of the protein machinery for oxidative phosphorylation (OXPHOS) for energy production. Therefore, the number of mitochondria and the correlation of their activity with the cellular mechanisms that regulate growth, nutrient availability, and cell homeodynamics are tightly regulated. However, the mechanistic details of these processes remain unknown.Mitochondria consist of two membranes, the Outer Mitochondrial Membrane (OMM) and the Inner Mitochondrial Membrane (IMM). Being dynamic cellular structures, mitochondria rapidly remodel their shape and size through the processes of fusion and fission. In mammals, the fusion process is regulated by the proteins Mfn1, Mfn2, and Opa1. Mfn proteins participate in OMM fusion, while Opa1 is involved in IMM fusion and cristae remodeling. Mitochondrial fusion is an evolutionarily conserved process that enables the change of mitochondrial structure as well as the exchange of mitochondrial material. The Opa1 protein is essential for the completion of the fusion, allowing the fusion of the IMM, the regulation of the biogenesis and cristae remodeling of the mitochondrial, and the release of cytochrome c during apoptosis. Fission is the other dynamic process of mitochondria, by which two or more mitochondria are created – a major mediator of fission is the Drp1 protein. Mitochondrial mass and activity must be adjusted in response to the regulation of tissue homeostasis, cell growth rates, and nutrient availability. In mammals, the ...