Friday, March 31, 2023
Mitochondrial Health

Nuclear transcription regulation of mitochondrial biogenesis

According to some estimates, each neuron can have up to 2 million mitochondria. A small but growing number of scientists are now turning their attention to the contributions of mitochondria in brain health. Jun 18, 2021

Mitochondria are highly dynamic organelles that divide, fuse, and move purposefully within axons and dendrites. Major functions of mitochondria in neurons include the regulation of Ca2+ and redox signaling, developmental and synaptic plasticity, and the arbitration of cell survival and death. Dec 10, 2008

Calcium is thought to play an important role in regulating mitochondrial function. Evidence suggests that an increase in mitochondrial calcium can augment ATP production by altering the activity of calcium-sensitive mitochondrial matrix enzymes. May 22, 2015

Ca2+ accumulation into the mitochondria stimulates aerobic metabolism and thus ATP production by modulating the activity of the enzymes of the tricarboxylic acid cycle (TCA cycle) and other effectors. Mitochondrial Ca2+ waves control cell fate.

Recent evidence demonstrates that mitochondria also actively participate in numerous biological processes by acting as initiators and transducers of cell signalling. In general, mitochondria regulate cell signalling through two means: serving as physical platforms on which protein–protein signalling interactions occur, and by regulating the levels of intracellular signalling molecules, including Ca2+ and reactive oxygen species (ROS). Consequently, mitochondria have been implicated in the regulation of various processes, including growth factor signalling, differentiation and hypoxic stress responses.

Mitochondrial biogenesis is a major adaption of skeletal muscle to exercise training and is induced by a complex interplay between numerous signaling pathways that respond to metabolic, mechanical, and hypoxic stresses that are generated within the myocyte during contraction.

Regulatory pathways involved in mitochondrial biogenesis.

Mitochondrial biogenesis is activated via cellular stress or in response to environmental stimuli. PGC-1α is the main regulator of mitochondrial biogenesis and activated via AMPK, SIRT1, eNOS, SIRTs, TORCs, and AMPK increase the PGC-1α gene transcription, which resulting enhanced NRFs. Endothelial NO synthase (eNOS) display an increase in mtDNA content, cytochrome c, as well as PGC-1α, NRF-1, and Tfam mRNA expression.

Nuclear transcription regulation

Mitochondrial biogenesis is orchestrated by specific nuclear transcription factors that regulate the expression of genes encoding mitochondrial proteins. Jul 27, 2016

Regulation of mitochondrial biogenesis

eNOS, SIRTs, TORCs, AMPK and possibly CaMKIV cause an increase in PGC-1α gene transcription, which results in an increase in NRFs, leading to mtDNA …

The main pathways of mitochondrial energy metabolism in cells are glycolysis, TCA cycle, and OXPHOS. Glycolysis and the TCA cycle produce reduced nicotinamide adenine dinucleotide (NADH), reduced flavin adenine dinucleotide, and other energetic molecules; while OXPHOS uses these substances to reduce O2 and release energy to synthesise ATP.

At the molecular level, mitochondrial fusion is positively regulated by mitofusin proteins (MFN1 and MFN2) and negatively regulated by the fission-promoting proteins DRP1 and FIS1 (Castanier et al., 2010; Onoguchi et al., 2010; Yasukawa et al., 2009). Interestingly, MFN2 interacts with MAVS and its overexpression inhibits RLR signalling.

RIG-like receptors (retinoic acid-inducible gene-I-like receptors, RLRs) are a type of intracellular pattern recognition receptor.

The activity of RLRs is controlled by several mechanisms that include PTMs mediated by regulatory enzymes; regulation by interacting proteins (for example, co-receptor molecules); post-transcriptional mechanisms, in particular cellular non-coding RNAs; and autophagy. Mar 13, 2020


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