Transcriptional Regulation of Mitochondrial Biogenesis and Quality Control
The capacity of a cell to renew or expand its mitochondrial population is important for cell survival during periods of intensified energy demand or after episodes of cell damage, particularly in organs with high energy utilization rates, such as the liver. This response is regulated by a bigenomic transcriptional program of mitochondrial biogenesis modulated by energy- and redox-dependent signals that coordinate mitochondrial mass with cellular energy demand. Energy demand can change rapidly in response to varying physiological or pathological conditions, such as work, growth, proliferation, and differentiation, or by the need to repair cell damage, including mitochondria, for example, from inflammation. Such events stimulate the coordinated activities of several multifunctional transcription factors and coactivators also involved in the elimination of defective mitochondria, as part of a unified mitochondrial quality- and damage-control network. Here, we present current information on the modes of action of known transcription factors that comprise the transcriptional machinery for nuclear-encoded mitochondrial genes and the actions of mitochondrial transcription factors and nuclear receptors on regulatory regions of the mitochondrial DNA. The importance of mitochondrial quality control is emphasized in supporting a cell’s metabolic needs and improving its resistance to metabolic failure in the setting of inflammation and mitochondrial damage.
