Mitochondrial biogenesis through activation of nuclear signaling proteins

Abstract

The dynamics of mitochondrial biogenesis and function is a complex interplay of cellular and molecular processes that ultimately shape bioenergetics capacity. Mitochondrial mass, by itself, represents the net balance between rates of biogenesis and degradation. Mitochondrial biogenesis is dependent on different signaling cascades and transcriptional complexes that promote the formation and assembly of mitochondria--a process that is heavily dependent on timely and coordinated transcriptional control of genes encoding for mitochondrial proteins. In this article, we discuss the major signals and transcriptional complexes, programming mitochondrial biogenesis, and bioenergetic activity. This regulatory network represents a new therapeutic window into the treatment of the wide spectrum of mitochondrial and neurodegenerative diseases characterized by dysregulation of mitochondrial dynamics and bioenergetic deficiencies.

Figure 1.

An overview of the transcriptional complexes regulating mitochdondrial gene expression and the signaling pathways converging upon them. Illustrated are the major transcriptional complexes/chromatin remodeling factors directly associated with changes in mitochondrial gene expression (see text for additional information).

Figure 2.

Transcriptional control of processes involved in the regulation of mitochondrial dynamics. Nuclear transcription factors regulate the transcription of specific proteins that are basic components of specific mitochondrial processes associated with mitochondrial dynamics (see text for further information).