Mitochondria—Striking a balance between host and endosymbiont

Abstract

Mitochondria are organelles with their own genome that arose from α-proteobacteria living within single-celled Archaea more than a billion years ago. This step of endosymbiosis offered tremendous opportunities for energy production and metabolism and allowed the evolution of fungi, plants, and animals. However, less appreciated are the downsides of this endosymbiosis. Coordinating gene expression between the mitochondrial genomes and the nuclear genome is imprecise and can lead to proteotoxic stress. The clonal reproduction of mitochondrial DNA requires workarounds to avoid mutational meltdown. In metazoans that developed innate immune pathways to thwart bacterial and viral infections, mitochondrial components can cross-react with pathogen sensors and invoke inflammation. Here, I focus on the numerous and elegant quality control processes that compensate for or mitigate these challenges of endosymbiosis.

Synergism and antagonism of two distinct, but confused, Nrf1 factors in integral regulation of the nuclear-to-mitochondrial respiratory and antioxidant transcription networks

“…In this genome, only 13 mitochondrial genes encode proteins as essential subunits of the respiratory chain, whilst the remaining 24 genes encode specific tRNA and rRNA required for its protein translation within the mitochondrial matrix (8,9). Such a small complement of mitochondrial genes exists over the entire evolutionary process to strike a balance between the host and its endosymbionts (10,11).…”

“…Aside from only 13 mitochondrially-encoded per se proteins (9), all other thousands of the host nucleus-encoded mitochondrial proteins for its biogenesis, structure and functions in the cellular respiration, oxidative phosphorylation, energy metabolism and redox balance are subjected to their temporospatial precision expression (10,28). Of note, a considerable number of the nucleus-encoded mitochondrial proteins are transcriptionally regulated by -Pal NRF1 and GABP NRF2 (26,27), and also translationally monitored by -Pal NRF1 -targeted eIF2 (21)(22)(23).…”

coil: an R package for cytochrome C oxidase I (COI) DNA barcode data cleaning, translation, and error evaluation

“…As a result of its ancient endosymbiotic origin, mitochondrial translation utilizes a different 143 genetic code from the nucleus, and this code additionally varies across taxa (Youle 2019). The coil 144 package is therefore designed in a manner robust to the variability in animal mitochondrial genetic 145 codes (NCBI numeric identifiers: 2, 4, 5, 9, 13, 14, 21, 24, and 33) (Elzanowski and Ostell 2019).…”

MitophAging: Mitophagy in Aging and Disease

“…Increased evidence indicates that mitochondrial integrity is disrupted during the aging process and contributes to the pathogenesis of age-related disorders in humans (Kauppila et al, 2017;Youle, 2019). In line with this, mice that carry a defective proof-reading mitochondrial DNA polymerase gamma show an accelerated aging phenotype that may be driven by the accumulation of mutations in the mitochondrial DNA (mtDNA) (Trifunovic et al, 2004).…”