Mitochondrial fusion, fission, and mitochondrial toxicity

Abstract

Mitochondrial dynamics are regulated by two sets of opposed processes: mitochondrial fusion and fission, and mitochondrial biogenesis and degradation (including mitophagy), as well as processes such as intracellular transport. These processes maintain mitochondrial homeostasis, regulate mitochondrial form, volume and function, and are increasingly understood to be critical components of the cellular stress response. Mitochondrial dynamics vary based on developmental stage and age, cell type, environmental factors, and genetic background. Indeed, many mitochondrial homeostasis genes are human disease genes. Emerging evidence indicates that deficiencies in these genes often sensitize to environmental exposures, yet can also be protective under certain circumstances. Inhibition of mitochondrial dynamics also affects elimination of irreparable mitochondrial DNA (mtDNA) damage and transmission of mtDNA mutations. We briefly review the basic biology of mitodynamic processes with a focus on mitochondrial fusion and fission, discuss what is known and unknown regarding how these processes respond to chemical and other stressors, and review the literature on interactions between mitochondrial toxicity and genetic variation in mitochondrial fusion and fission genes. Finally, we suggest areas for future research, including elucidating the full range of mitodynamic responses from low to high-level exposures, and from acute to chronic exposures; detailed examination of the physiological consequences of mitodynamic alterations in different cell types; mechanism-based testing of mitotoxicant interactions with interindividual variability in mitodynamics processes; and incorporating other environmental variables that affect mitochondria, such as diet and exercise.

Predictors of mitochondrial DNA copy number and damage in a mercury‐exposed rural Peruvian population near artisanal and small‐scale gold mining: An exploratory study

“…Damage can also be diluted by mtDNA biogenesis, which acts in concert with mitophagy to regulate mtDNA CN. Similarly, mitochondrial stress can trigger both mtDNA replication and degradation (Meyer et al, ). Finally, any changes in the half‐lives of the various populations of cell types that “WBCs” comprise could lead to alterations in these parameters, since the removal and replacement of cells implies replacement of mitochondrial genomes.…”

Biological links in periodontitis and rheumatoid arthritis: Discovery via text‐mining PubMed abstracts

“…Damage of organelle machinery is associated with chronic inflammation . Mitochondrial damage in particular, releases damage‐associated molecular patterns (DAMP) causing activation of pattern recognition receptors (PRR) . RA patients have higher levels of mitochondrial fission products in plasma and synovial fluid .…”

“…77 nodes were represented recognition receptors (PRR). 40 RA patients have higher levels of mitochondrial fission products in plasma and synovial fluid. 41 The DAMP cell-free mitochondrial DNA in circulation is emerging as an inflammatory and prognostic marker in multiple diseases.…”

Organelle dynamics and viral infections: at cross roads

“…Mitochondrial morphology is maintained by a series of interlinked events namely mitochondrial fusion, fission and mitophagy [78]. Mitochondrial fusion helps in exchanging matrix metabolites and intact mitochondrial DNA while mitochondrial fission helps in sorting impaired mitochondria from the healthy population which are further eliminated by a process called mitophagy [79]. All the above dynamic events are altered upon viral infection in order to facilitate its replication (Fig.…”