The influence of mitochondrial dynamics on mitochondrial genome stability

Prevost, Christopher T; Peris, Nicole; Seger, Christina; Pedeville, Deanna; Wershing, Kathryn C.; Sia, Elaine A.; Sia, Rey A. L.

doi:10.1007/s00294-017-0717-4

Cited by 18 publications

(10 citation statements)

References 56 publications

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“…Mitochondrial repair and recycling are often referred to as mitochondrial dynamics: an elegant process of fusion (joining), fission (separation), biogenesis (synthesis of new mitochondria) and mitophagy (clearance of dysfunctional mitochondria) to adapt to a constantly changing environment (51). As this mechanism is critical to mitochondrial function and thereby cellular and tissue health, any alteration to such a process has direct consequences on organ function (51,67,109). Recently it has been shown that changes to mitochondrial dynamics resulting in fragmentation, swollen and large mitochondria which cannot undergo mitophagy are indicative of ageing (51).…”

Section: Mitochondrial Dynamics and Placental Ageingmentioning

confidence: 99%

Mitochondrial transformations in the aging human placenta

Bartho

Fisher

Cuffe

et al. 2020

American Journal of Physiology-Endocrinology and Metabolism

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Mitochondria play a key role in homeostasis and are central to one of the leading hypotheses of ageing, the free radical theory. Mitochondria function as a reticulated network, constantly adapting to the cellular environment through fusion (joining), biogenesis (formation of new mitochondria) and fission (separation). This adaptive response is particularly important in response to oxidative stress, cellular damage and ageing, when mitochondria are selectively removed through mitophagy, a mitochondrial equivalent of autophagy. During this complex process, mitochondria influence surrounding cell biology and organelles through the release of signalling molecules. Given that the human placenta is a unique organ having a transient and somewhat defined lifespan of approximately 280 days, any adaption or dysfunction associated with mitochondrial physiology as a result of ageing will have a dramatic impact on the health and function of both the placenta and the fetus. Additionally, a defective placenta during gestation, resulting in reduced fetal growth, has been shown to influence the development of chronic disease in later life. In this review we focus on the mitochondrial adaptions and transformations which accompany gestational length and share similarities with aged related diseases. In addition, we will discuss the role of such changes in regulating placental function throughout gestation, the aetiology of gestational complications and in the development of chronic diseases later in life.

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Section: Mitochondrial Dynamics and Placental Ageingmentioning

confidence: 99%

Mitochondrial transformations in the aging human placenta

Bartho

Fisher

Cuffe

et al. 2020

American Journal of Physiology-Endocrinology and Metabolism

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“…The structural diversity of the recombinant mitochondrial genomes can be ascribed to recombination events at random positions. The intensifying research into yeast mitochondrial biology (e.g., Wu et al, 2015;Higuchi-Sanabria et al, 2016;Pernice et al, 2016Pernice et al, , 2018Chakraborty et al, 2017;Guaragnella et al, 2018;Prevost et al, 2018;Ling et al, 2019;Dhar et al, 2019;Peris et al, 2019) will surely provide novel tools for the deciphering of the complexity of the mechanisms underlying the transmission of the mitochondrial genomes into the hybrid bud formed on the zygote and their subsequent evolution.…”

Section: Hybrid Homoplasmymentioning

confidence: 99%

Diversity and Postzygotic Evolution of the Mitochondrial Genome in Hybrids of Saccharomyces Species Isolated by Double Sterility Barrier

et al. 2020

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Eukaryotic species are reproductively isolated by sterility barriers that prevent interspecies fertilization (prezygotic sterility barrier) or the fertilization results in infertile offspring (postzygotic sterility barrier). The Saccharomyces species are isolated by postzygotic sterility barriers. Their allodiploid hybrids form no viable gametes (ascospores) and the viable ascospores of the allotetraploids cannot fertilize (conjugate). Our previous work revealed that this mechanism of reproductive isolation differs from those operating in plants and animals and we designated it double sterility barrier (the failure of homeologous chromosomes to pair and the repression of mating by matingtype heterozygosity). Other studies implicated nucleo-mitochondrial incompatibilities in the sterility of the Saccharomyces hybrids, a mechanism assumed to play a central role in the reproductive isolation of animal species. In this project the mitochondrial genomes of 50 cevarum (S. cerevisiae × S. uvarum) hybrids were analyzed. 62% had S. cerevisiae mitotypes, 4% had S. uvarum mitotypes, and 34% had recombinant mitotypes. All but one hybrid formed viable spores indicating that they had genomes larger than allodiploid. Most of these spores were sterile (no sporulation in the clone of vegetative descendants; a feature characteristic of allodiploids). But regardless of their mitotypes, most hybrids could also form fertile alloaneuploid spore clones at low frequencies upon the loss of the MAT-carrying chromosome of the S. uvarum subgenome during meiosis. Hence, the cevarum alloploid nuclear genome is compatible with both parental mitochondrial genomes as well as with their recombinants, and the sterility of the hybrids is maintained by the double sterility barrier (determined in the nuclear genome) rather than by nucleo-mitochondrial incompatibilities. During allotetraploid sporulation both the nuclear and the mitochondrial genomes of the hybrids could segregate but no correlation was observed between the sterility or the fertility of the spore clones and their mitotypes. Nucleo-mitochondrial incompatibility was manifested as respiration deficiency in certain meiotic segregants. As respiration is required for meiosis-sporulation but not for fertilization (conjugation), these segregants were deficient only in sporulation. Thus, the nucleo-mitochondrial incompatibility affects the sexual processes only indirectly through the inactivation of respiration and causes only partial sterility in certain segregant spore clones.

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“…Dnm1 is recruited to mitochondria by co-factors: Fis1, a protein in the mitochondrial outer membrane (Mozdy et al 2000), and Mdv1 that binds to both Fis1 and Dnm1 and brings them together (Cerveny and Jensen 2003; Cerveny et al 2001; Karren et al 2005; Tieu and Nunnari 2000; Tieu et al 2002). Saccharomyces cerevisiae deletion mutants in DNM1, FIS1 or MDV1 display a mitochondrial fission defect, resulting in the formation of long, hyper-connected mitochondria, and also have some other cellular phenotypes related to fitness, as well as organelle and membrane structure and contacts (Dimmer et al 2002; Elbaz-Alon et al 2014; Gorsich and Shaw 2004; Kanki et al 2009; Prevost et al 2018; Qian et al 2012). Deletion of CAF1 , a paralog of MDV1 , does not cause a fission defect by itself, but it potentiates the defect of mdv1 mutants (Griffin et al 2005).…”

Section: Mitochondrial Fission In Pathogenic Fungal Speciesmentioning

confidence: 99%

Mdivi-1 and mitochondrial fission: recent insights from fungal pathogens

Koch

Traven

2019

Curr Genet

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Mitochondrial fission shows potential as a therapeutic target in non-infectious human diseases. The compound mdivi-1 was identified as a mitochondrial fission inhibitor that acts against the evolutionarily conserved mitochondrial fission GTPase Dnm1/Drp1, and shows promising data in pre-clinical models of human pathologies. Two recent studies, however, found no evidence that mdivi-1 acts as a mitochondrial fission inhibitor and proposed other mechanisms. In mammalian cells, Bordt et al. showed that mdivi-1 inhibits complex I in mitochondria (Dev Cell 40:583, 2017). In a second study, we have recently demonstrated that mdivi-1 does not trigger a mitochondrial morphology change in the human yeast pathogen Candida albicans , but impacts on endogenous nitric oxide (NO) levels and inhibits the key virulence property of hyphal formation (Koch et al., Cell Rep 25:2244, 2018). Here we discuss recent insights into mdivi-1’s action in pathogenic fungi and the potential and challenges for repurposing it as an anti-infective. We also outline recent findings on the roles of mitochondrial fission in human and plant fungal pathogens, with the goal of starting the conversation on whether the research field of fungal pathogenesis can benefit from efforts in other disease areas aimed at developing therapeutic inhibitors of mitochondrial division.

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The influence of mitochondrial dynamics on mitochondrial genome stability

Cited by 18 publications

References 56 publications

Mitochondrial transformations in the aging human placenta

Mitochondrial transformations in the aging human placenta

Diversity and Postzygotic Evolution of the Mitochondrial Genome in Hybrids of Saccharomyces Species Isolated by Double Sterility Barrier

Mdivi-1 and mitochondrial fission: recent insights from fungal pathogens

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