Whole Cell Cryo-Electron Tomography Suggests Mitochondria Divide by Budding

Hu, Guobin

doi:10.1017/s1431927614001317

Cited by 12 publications

(14 citation statements)

References 44 publications

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“…Visual inspection of the mitochondria within the individual micrographs from patient and control cells revealed both spherical and tubular/elongated mitochondria, with closely apposed MIM and MOM, and an electron-dense matrix containing cristae and calcium/phosphorus ion granules ( Wolf et al., 2017 ) ( Figure S2 ). The appearance of these mitochondria was comparable to previous reports of in situ human mitochondria ( Hu, 2014 ) and consistent across both our patient and control samples. In addition, we found that the signal-to-noise ratio is considerably lower for in situ datasets compared with prior work using purified mitochondria ( Nicastro et al., 2000 ), as reflected in such parameters as mitochondrial matrix texture.…”

Section: Resultssupporting

confidence: 91%

Three-Dimensional Analysis of Mitochondrial Crista Ultrastructure in a Patient with Leigh Syndrome by In Situ Cryoelectron Tomography

et al. 2018

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SummaryMitochondrial diseases produce profound neurological dysfunction via mutations affecting mitochondrial energy production, including the relatively common Leigh syndrome (LS). We recently described an LS case caused by a pathogenic mutation in USMG5, encoding a small supernumerary subunit of mitochondrial ATP synthase. This protein is integral for ATP synthase dimerization, and patient fibroblasts revealed an almost total loss of ATP synthase dimers. Here, we utilize in situ cryoelectron tomography (cryo-ET) in a clinical case-control study of mitochondrial disease to directly study mitochondria within cultured fibroblasts from a patient with LS and a healthy human control subject. Through tomographic analysis of patient and control mitochondria, we find that loss of ATP synthase dimerization due to the pathogenic mutation causes profound disturbances of mitochondrial crista ultrastructure. Overall, this work supports the crucial role of ATP synthase in regulating crista architecture in the context of human disease.

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Section: Resultssupporting

confidence: 91%

Three-Dimensional Analysis of Mitochondrial Crista Ultrastructure in a Patient with Leigh Syndrome by In Situ Cryoelectron Tomography

et al. 2018

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“…[1][2][3]34 Recent observations based on cell cryoelectron tomography indicate that budding is the mitochondrial division mechanism. 59 Budding is also known in bacterial endospores, 60,61 and membraneenveloped viruses, 62-65 such as Poxviridae. Hence, the process of mitochondrial division also hints at possible origins of mitochondria and viruses from bacterial endospores.…”

Section: Cellular Origin Of Virusesmentioning

confidence: 99%

Giant viruses: spore‐like missing links between Rickettsia and mitochondria?

Seligmann

2019

Annals of the New York Academy of Sciences

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Phyloproteomics indicate common viral origin from ancient cells before archaea, bacteria, and eukaryota split and subsequent size and complexity reductions occurred. Further independent evidence for the cellular origin of viruses is reviewed for the virus order Megavirales, focusing on the family Poxviridae. Megavirales comprises giant viruses, double‐stranded DNA viruses whose genomes exceed some bacterial ones and large enough to parasitize large‐celled protists (amoeba). Giant viruses, virophages, and mitochondria have homologous DNA and RNA polymerases and share RNA splicing punctuation by stem–loop hairpins. Giant virus factories and amoeban mitochondria colocate, with viral proteins homologous to mitochondrial proteins specifically targeting mitochondrial inner membranes. Mitochondria share asexual budding with many bacterial endospores and membrane‐enveloped viruses. These megavirus−mitochondrion similarities are not coincidental: systematic alignment analyses have detected candidate megaviral homologs of each amoeban mitogene (including ribosomal RNAs) distributed across megaviral genomes. These candidate megaviral homologs overall follow mitogene order, and megaviral−mitogenome synteny increases with viral genome reduction. This analysis is repeated within Poxviridae, whose organellar‐like morphogenesis is reminiscent of mitochondria. More generally, the results confirm the patterns observed in Megavirales: synteny with amoeban mitogenomes increases with genome reduction. Parsimoniously interpreting this suggests Megavirales and mitochondria have a rickettsia‐like common ancestor. Megavirales could be the missing links between bacterial‐like cells and mitochondria, implying cellular‐to‐viral‐to‐subcellular macroevolution.

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“…3e, SI). The mitochondrial envelope is composed of two membranes, which are constrained to be in close proximity at the constriction site [32]. Thus, as a first approximation, we considered both membranes as a composite system with a rigidity of 40 kBT, double the value of single lipid bilayers from in vitro measurements [33].…”

Section: Fission Events Are Characterized By Higher Bending Energymentioning

confidence: 99%

Mitochondrial membrane tension governs fission

Mahecic

Carlini

Kleele

et al. 2018

Preprint

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2Mitochondria rely on cellular machinery for their division, which is an essential component of metabolic response of the cell. Many division factors have been identified; however, a framework accounting for the energetic requirements of the mitochondrial fission process is lacking. We report that the presence of an active constriction does not ensure fission. Instead, by measuring constrictions down to ~100 nm with time-lapse super-resolution microscopy, we found that 34% of constrictions failed to divide and 'reversed' to an unconstricted state. Higher local curvaturesreflecting an increased bending energy -made constriction sites more likely to divide, but often with a significant residual energy barrier to fission. Our data suggest that membrane tension, largely arising from pulling forces, could account for this missing energy. These results lead us to propose that mitochondrial fission is probabilistic, and can be modeled as arising from bending energy complemented by a fluctuating membrane tension.Mitochondria are highly dynamic organelles, transported through the cytoplasm along cytoskeletal networks as they change in size and shape. Mitochondrial morphologies can range from a filamentous, connected network to a fragmented collection of individuals. Underlying such morphological changes are altered equilibria between fusion and division 1,2 . These transformations have been linked to an adaptive response to cellular energy requirements, for example in response to stress [3][4][5] or the cell cycle 6 . As a vestige of their bacterial origins, mitochondria cannot be generated de novo, but must multiply by division, or fission, of existing mitochondria 7 . Division has also been suggested to act as part of a quality control mechanism 8,9 and an intracellular signal for mitophagy 10,11 .All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/255356 doi: bioRxiv preprint first posted online 3 In bacterial division systems, internal assembly of the fission machinery is tightly regulated and a series of cell cycle checkpoints ensure daughter cell viability. In contrast, the mitochondrial division machinery is external to the organelle, allowing cells to flexibly regulate fission. Initially, the division site is marked by a pre-constriction defined by contact with ER tubules 12 and deformed by targeted actin polymerization [13][14][15] Live-cell Structured Illumination Microscopy (SIM) of Drp1-mediated mitochondrial constriction events enabled us to measure dynamic changes in membrane geometry leading up to and following division. We discovered that a fraction of mitochondria constrict dramatically before relaxing to an unconstricted state, termed 'reversals'. Using a custom-written image analysis package and classical elasticity theory, we calculated the energy differences between fission and reversal events, which al...

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Whole Cell Cryo-Electron Tomography Suggests Mitochondria Divide by Budding

Cited by 12 publications

References 44 publications

Three-Dimensional Analysis of Mitochondrial Crista Ultrastructure in a Patient with Leigh Syndrome by In Situ Cryoelectron Tomography

Three-Dimensional Analysis of Mitochondrial Crista Ultrastructure in a Patient with Leigh Syndrome by In Situ Cryoelectron Tomography

Giant viruses: spore‐like missing links between Rickettsia and mitochondria?

Mitochondrial membrane tension governs fission

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