Mitochondrial proteins: from biogenesis to functional networks

Pfanner, Nikolaus; Warscheid, Bettina; Wiedemann, Nils

doi:10.1038/s41580-018-0092-0

Cited by 731 publications

(590 citation statements)

References 272 publications

(298 reference statements)

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“…Following insults to the myelin, adaptive mechanisms do occur in the axons as chronically demyelinated and remyelinated axons display higher mitochondria density compared to homeostatic conditions [1,20,29]. Similar, mitochondrial adaptation mechanisms have also been observed outside the CNS where mitochondria growth/enlargement is an accepted proxy for cellular adaption to increased energy demand and/or a detrimental response to cellular stress and Bax/Bcl [15,21,26]. Suggestively, the myelin sheath thickness and metabolic axonal features influence each other during myelin repair but also during homeostatic conditions [4,5,9].…”

Section: Introductionmentioning

confidence: 92%

Axonal mitochondria across species adjust in diameter depending on thickness of surrounding myelin

Ineichen

Zhu

Carlström

2019

Preprint

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In the central nervous system (CNS), axons and its surrounding myelin sheaths, generated by oligodendrocytes, greatly depend on each other, where oligodendrocytes provide axons with both trophic and metabolic support. Across spices, assessment of the axon-myelin ultrastructure is the key-approach to visualize de-and re-myelination of axons. However, this assessment omits to provide information on axonal homeostasis or how axon-myelin influence one another. Since mitochondria may adjust in size thus mirroring the intracellular physiological and metabolic status we applied this to myelinated axons in the CNS. We herein show that a large axonal mitochondria diameter correlates with thinner surrounding myelin sheaths across different CNS tracts and species, including human. We also show that the relation between axonal mitochondria diameter and surrounding myelin thickness is a valuable measurement to verify advanced remyelination in two commonly used experimental demyelinating models, namely the cuprizone and the lysolecithin (LPC) model. Lastly, we show that axonal mitochondria adjust in diameter in response to the thickness of the axonal surrounding myelin whereas the opposite adaption was absent. In summary, the link between axonal mitochondria diameter and surrounding myelin thickness provide insight on the axon-myelin relation both during homeostasis and pathological conditions. This link is also translational applicable and can thus contribute to a better understanding on how to study remyelination using experimental models.

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Section: Introductionmentioning

confidence: 92%

Axonal mitochondria across species adjust in diameter depending on thickness of surrounding myelin

Ineichen

Zhu

Carlström

2019

Preprint

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“…Protein import into mitochondria has been more extensively studied in yeast and other fungi (Pfanner et al, 2019;Wiedemann and Pfanner, 2017;Neupert, 2015). For example, the insertion of beta-barrel membrane proteins into the mitochondrial outer membrane involves the TOM complex (translocase of the outer mitochondrial membrane complex) and the SAM complex (sorting and assembly machinery complex).…”

Section: Introductionmentioning

confidence: 99%

Metaxin 3 is a Highly Conserved Vertebrate Protein Homologous to Mitochondrial Import Proteins and GSTs

Adolph

2019

Preprint

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Metaxin 3 genes are shown to be widely conserved in vertebrates, including mammals, birds, fish, amphibians, and reptiles. Metaxin 3 genes, however, are not found in invertebrates, plants, and bacteria. The predicted metaxin 3 proteins were identified by their homology to the metaxin 3 proteins encoded by zebrafish and Xenopus cDNAs. Further evidence that they are metaxin proteins was provided by the presence of GST_N_Metaxin, GST_C_Metaxin, and Tom37 protein domains, and the absence of other major domains. Alignment of human metaxin 3 and human metaxin 1 predicted amino acid sequences showed 45% identities, while human metaxin 2 had 23% identities. These results indicate that metaxin 3 is a distinct metaxin. A wide variety of vertebrate species-including human, zebrafish, Xenopus, dog, shark, elephant, panda, and platypus-had the same genes adjacent to the metaxin 3 gene. In particular, the thrombospondin 4 gene (THBS4) is next to the metaxin 3 gene (MTX3). By comparison, the thrombospondin 3 gene (THBS3) is next to the metaxin 1 gene (MTX1). Phylogenetic analysis showed that metaxin 3, metaxin 1, and metaxin 2 protein sequences formed separate clusters, but with all three metaxins being derived from a common ancestor. Alpha-helices dominate the predicted secondary structures of metaxin 3 proteins. Little beta-strand is present. The pattern of 9 helical segments is also found for metaxins 1 and 2.Abbreviations: MTX3, metaxin 3; MTX1, metaxin 1; MTX2, metaxin 2

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“…The import of proteins into mitochondria has been investigated in great detail in yeast (Saccharomyces cerevisiae) (Pfanner et al, 2019;Wiedemann and Pfanner, 2017;Neupert, 2015).…”

Section: Introductionmentioning

confidence: 99%

Invertebrate Metaxins 1 and 2: Widely Distributed Proteins Homologous to Vertebrate Metaxins Implicated in Protein Import into Mitochondria

Adolph

2020

Preprint

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Metaxin 1 and 2 genes, previously investigated in vertebrates, are shown to be widely distributed among invertebrates. But metaxin 3 is absent. The predicted proteins of the invertebrate metaxins were initially identified by homology with human metaxin 1 and 2 proteins, and by the presence of characteristic GST_Metaxin protein domains. Invertebrate metaxins were revealed for a variety of phyla, including Echinodermata, Cnidaria, Porifera, Chordata, Arthropoda, Mollusca, Brachiopoda, Placozoa, and Nematoda. Metaxins were also found in insects (Arthropoda) of different taxonomic orders: Diptera, Coleoptera, Lepidoptera, Hymenoptera, and Blattodea. Invertebrate and human metaxin 1 proteins have about 41% identical amino acids, while metaxin 2 proteins have about 49% identities. Invertebrate and vertebrate metaxins share the same characteristic protein domains, further strengthening the identification of the invertebrate proteins as metaxins. The domains are, for metaxin 1, GST_N_Metaxin1_like, GST_C_Metaxin1_3, and Tom37. For metaxin 2, they are GST_N_Metaxin2, GST_C_Metaxin2, and Tom37. Phylogenetic trees show that invertebrate metaxin 1 and metaxin 2 proteins are related, but form separate groups. The invertebrate proteins are also closely related to vertebrate metaxins, though forming separate clusters. These phylogenetic results indicate that all metaxins likely arose from a common ancestral sequence. The neighboring genes of the invertebrate metaxin 1 and 2 genes are largely different for different invertebrate species. This is unlike the situation with vertebrate metaxin genes, where, for example, the metaxin 1 gene is adjacent to the thrombospondin 3 gene. The dominant secondary structures predicted for the invertebrate metaxins are alpha-helical segments, with little beta-strand. The conserved pattern of helical segments is the same as that found for vertebrate metaxins 1, 2, and 3.

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Mitochondrial proteins: from biogenesis to functional networks

Cited by 731 publications

References 272 publications

Axonal mitochondria across species adjust in diameter depending on thickness of surrounding myelin

Axonal mitochondria across species adjust in diameter depending on thickness of surrounding myelin

Metaxin 3 is a Highly Conserved Vertebrate Protein Homologous to Mitochondrial Import Proteins and GSTs

Invertebrate Metaxins 1 and 2: Widely Distributed Proteins Homologous to Vertebrate Metaxins Implicated in Protein Import into Mitochondria

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