Starting the engine of the powerhouse: mitochondrial transcription and beyond

Abstract

Mitochondria are central hubs for cellular metabolism, coordinating a variety of metabolic reactions crucial for human health. Mitochondria provide most of the cellular energy via their oxidative phosphorylation (OXPHOS) system, which requires the coordinated expression of genes encoded by both the nuclear (nDNA) and mitochondrial genomes (mtDNA). Transcription of mtDNA is not only essential for the biogenesis of the OXPHOS system, but also generates RNA primers necessary to initiate mtDNA replication. Like the prokaryotic system, mitochondria have no membrane-based compartmentalization to separate the different steps of mtDNA maintenance and expression and depend entirely on nDNA-encoded factors imported into the organelle. Our understanding of mitochondrial transcription in mammalian cells has largely progressed, but the mechanisms regulating mtDNA gene expression are still poorly understood despite their profound importance for human disease. Here, we review mechanisms of mitochondrial gene expression with a focus on the recent findings in the field of mammalian mtDNA transcription and disease phenotypes caused by defects in proteins involved in this process.

Ribonucleotide synthesis by NME6 fuels mitochondrial gene expression

“…3B, S3A), which argues against NME6 being required for mitoribosome assembly. Mitochondrial transcription is initiated from a single promoter on the heavy-strand and two promoters on the light-strands of mtDNA to yield polycistronic transcripts that are further processed to individual mitochondrial messenger (m)RNAs, transfer (t)RNAs and ribosomal (r)RNAs 55,56 (Fig. 4D).…”

Differential Susceptibility of Retinal Neurons to the Loss of Mitochondrial Biogenesis Factor Nrf1

“…Mitochondria biogenesis is a subcellular process through which mitochondria are replenished and remodeled through continuously importing and incorporating new proteins and lipids, replicating mitochondrial DNA, transcribing mitochondrion-encoded genes, and fusing and dividing in response to cellular demands and bioenergetics loads. This process is essential for maintaining a healthy and functional mitochondria network for energy metabolism, calcium homeostasis, biosynthesis of amino acids, cholesterol, and phospholipids, eliminating excessive reactive oxygen species, and apoptosis [ 1 , 2 , 3 , 4 , 5 , 6 ].…”

Macrophage Mitochondrial Biogenesis and Metabolic Reprogramming Induced by Leishmania donovani Require Lipophosphoglycan and Type I Interferon Signaling

“…Analysis of the molecular mechanisms by which L. infantum modulates mitochondrial metabolism revealed an essential role for the metabolic sensor AMP-activated protein kinase (AMPK) ( 9 ), a key modulator of peroxisome proliferator-activated receptor gamma (PPARγ) coactivator 1α (PGC-1α) activity ( 11 , 12 ). PGC-1α is a transcriptional coactivator and is the master switch that integrates mitochondrial biogenesis and energy-generating functions of mitochondria with metabolic demands associated with physiological states associated with health and disease ( 13 – 16 ). Hence, PGC-1α controls multiple aspects of mitochondrial biogenesis, including increased mitochondrial number and biogenesis of the OXPHOS system ( 13 ), by coordinating the concerted expression of nuclear and mitochondrial genes encoding proteins involved in these processes ( 16 – 18 ).…”