The mobility of mitochondria: Intercellular trafficking in health and disease

Abstract

SummaryThe view that genes are constrained within somatic cells is challenged by in vitro evidence, and more recently by in vivo studies which demonstrate that mitochondria with their mitochondrial DNA (mtDNA) payload not only can, but do move between cells in tumour models and in mouse models of tissue damage. Using mouse tumour cell models without mtDNA to reflect mtDNA damage, we have shown that these cells | THE ORIGIN OF MITOCHONDRIARemarkable progress has been made over the last few years in firmly establishing the cellular origins of mitochondria present in almost all complex organisms. Although there is general consensus that the bacterium giving rise to mitochondria was an α-proteobacterium capable of using low levels oxygen present in the Proterozoic environment to generate chemical energy in the form of ATP, the nature of the engulfing organism has been more controversial. The discovery of Lokiarchaeota in deep sea sediments off the Icelandic coast 1 and subsequent elaboration of Asgard archaea 2 support the view that a highly evolved archaeal cell with many primitive eukaryotic features was the symbiont that hosted the mitochondrial precursor cell, and this appears to have been a singular event. It is noteworthy that both α-proteobacteria and archaea are capable forming pilli-like structures that transmit genetic material between cells, and that these properties

Mitostemness

“…Our mitostemness proposal is consistent with a number of descriptions in which the determination of cell fate involves the asymmetric distribution of certain mitochondrial controllers into CSC-like cell entities [84][85][86][87][88][89]. Indeed, our proposal complements the view that changes in intracellular, intercellular, and extracellular mitochondrial traffic [90][91][92][93][94] appear to ensure the functional endurance of mitochondria in the tumor-initiating and drug-resistant subpopulation of CSC. New therapeutics aimed to target mitochondria not only as biochemical but also as biophysical and morpho-physiological hallmarks of CSC might certainly guide improvements to cancer treatment.…”

Mitochondrial DNA: A Key Regulator of Anti-Microbial Innate Immunity

“…The transfer of mitochondria between cells has also been reported after ischemia-stimulated injury in the brain, heart, and lung epithelium [154,155]. The ability of mitochondrial transfer between cells seems to be an evolutionarily conserved event related to diseases with the compromised mitochondrial role, including neuromuscular, neurodegenerative, and cardiovascular diseases, aging, and cancer [156].…”

Aging mechanisms and intervention targets

“…Apart from exophers to remove damaged organelles in pathological spreading, studies show that mitochondria themselves with their own DNA genomes move between cells for intercellular mitochondrial transmission in tumour and in mouse models of tissue injuries (for review, see Berridge in this issue). Interestingly, cells devoid of mitochondrial DNA proliferate to form tumours only after acquiring mitochondrial DNA from cells in the local microenvironment .…”

“…Apart from exophers to remove damaged organelles in pathological spreading, studies show that mitochondria themselves with their own DNA genomes move between cells for intercellular mitochondrial transmission in tumour and in mouse models of tissue injuries (for review, see Berridge in this issue). Interestingly, cells devoid of mitochondrial DNA proliferate to form tumours only after acquiring mitochondrial DNA from cells in the local microenvironment . Mitochondrial transfer between cells can also occur following ischemia‐induced injury in the heart and brain and in lung epithelium following lung inflammation, with stem cells being the mitochondrial donors in response to situations as in aging .…”

“…Interestingly, cells devoid of mitochondrial DNA proliferate to form tumours only after acquiring mitochondrial DNA from cells in the local microenvironment . Mitochondrial transfer between cells can also occur following ischemia‐induced injury in the heart and brain and in lung epithelium following lung inflammation, with stem cells being the mitochondrial donors in response to situations as in aging . Thus, in cytoplasm aging, mitochondria operate by degrading cytoplasmic protein toxic aggregates, self‐recycling through mitophagy, and spreading pathogens to induce extracellular aging that is characteristic of SALI …”