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Mitochondrial biogenesis is the process by which cells increase mitochondrial numbers. [ 1 ] [ 2 ] It was first described by John Holloszy in the 1960s, when it was discovered that physical endurance training induced higher mitochondrial content levels, leading to greater glucose uptake by muscles. [ 3 ]
The human mitochondrial genome is the entirety of hereditary information contained in human mitochondria. Mitochondria are small structures in cells that generate energy for the cell to use, and are hence referred to as the "powerhouses" of the cell. Mitochondrial DNA (mtDNA) is not transmitted through nuclear DNA (nDNA).
PGC-1α provides a direct link between external physiological stimuli and the regulation of mitochondrial biogenesis, and is a major factor causing slow-twitch rather than fast-twitch muscle fiber types. [10] Endurance exercise has been shown to activate the PGC-1α gene in human skeletal muscle. [11]
Mitochondrial fatty acid synthesis (mtFASII) is essential for cellular respiration and mitochondrial biogenesis. [50] It is also thought to play a role as a mediator in intracellular signaling due to its influence on the levels of bioactive lipids, such as lysophospholipids and sphingolipids. [51]
The outer membrane mitochondrial proteins carry out functions for mitochondrial biogenesis and integration between mitochondria and the cellular system. The outer membrane consists of two types of integral proteins, including proteins with transmembrane β-barrel and proteins with one or more α-helical membrane anchors.
This means that mitochondrial DNA disorders may occur spontaneously and relatively often. Defects in enzymes that control mitochondrial DNA replication (all of which are encoded for by genes in the nuclear DNA) may also cause mitochondrial DNA mutations. Most mitochondrial function and biogenesis is controlled by nuclear DNA.
Mitogens can be either endogenous or exogenous factors. Endogenous mitogens function to control cell division is a normal and necessary part of the life cycle of multicellular organisms.
Nuclear respiratory factor 1, also known as Nrf1, Nrf-1, NRF1 and NRF-1, encodes a protein that homodimerizes and functions as a transcription factor which activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication.