Molecular genetic regulation of mitochondrial content: relative contributions of synthetic and degradative pathways
In higher eukaryotes, several fold differences in mitochondrial content (~2-20) are observed across tissues. While the divergent bioenergetic requirements of these tissues largely account for the observed variability, how certain tissues achieve and maintain these unique “set points” remains an open question. Equally unclear is why certain tissues have an inherently greater capacity to alter their mitochondrial content in response to environmental or physiological stimuli. One hypothesis is that the inter-tissue differences in mitochondrial content are explained by the differential regulation of pathways that contribute to organelle biogenesis and turnover.
Schematic of the relative contributions of synthetic and degradative pathways to the regulation of total mitochondrial content, both under basal conditions and during adaptive responses to chronic stimuli.
Using inbred mouse strains and transgenic animal models, the long-term objective of this research is to test this hypothesis. Defining the regulatory pathways that control mitochondrial content across tissues has important implications for our understanding of the physiological and evolutionary constraints relevant to the adaptive plasticity of the organelle. It may also offer mechanistic insight into what remains the mysterious, tissue-specific pathophysiology observed in patients presenting with mitochondrial diseases.