The Single Mitochondrial Porin of Trypanosoma brucei is the Main Metabolite Transporter in the Outer Mitochondrial Membrane

Pusnik, Mascha; Charrière, Fabien; Mäser, Pascal; Waller, Ross F.; Dagley, Michael J; Lithgow, Trevor; Schneider, André

doi:10.1093/molbev/msn288

Cited by 97 publications

(95 citation statements)

References 37 publications

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“…Characterizing protein-import machinery in phylogenetically diverse Euglenozoa would test this and whether its greater simplicity in trypanosomes (and I suggest all Euglenozoa) is primitive. On VDAC/Tom40 mitochondrial porin trees, the root of the VDAC half is precisely between Euglenozoa and neokaryotes (Pusnik et al 2009), as in my hypothesis.…”

Section: Where Is the Eukaryotic Root?mentioning

confidence: 61%

Kingdoms Protozoa and Chromista and the eozoan root of the eukaryotic tree

2009

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I discuss eukaryotic deep phylogeny and reclassify the basal eukaryotic kingdom Protozoa and derived kingdom Chromista in the light of multigene trees. I transfer the formerly protozoan Heliozoa and infrakingdoms Alveolata and Rhizaria into Chromista, which is sister to kingdom Plantae and arguably originated by synergistic double internal enslavement of green algal and red algal cells. I establish new subkingdoms (Harosa; Hacrobia) for the expanded Chromista. The protozoan phylum Euglenozoa differs immensely from other eukaryotes in its nuclear genome organization (trans-spliced multicistronic transcripts), mitochondrial DNA organization, cytochrome c -type biogenesis, cell structure and arguably primitive mitochondrial protein-import and nuclear DNA prereplication machineries. The bacteria-like absence of mitochondrial outer-membrane channel Tom40 and DNA replication origin-recognition complexes from trypanosomatid Euglenozoa roots the eukaryotic tree between Euglenozoa and all other eukaryotes (neokaryotes), or within Euglenozoa. Given their unique properties, I segregate Euglenozoa from infrakingdom Excavata (now comprising only phyla Percolozoa, Loukozoa, Metamonada), grouping infrakingdoms Euglenozoa and Excavata as the ancestral protozoan subkingdom Eozoa. I place phylum Apusozoa within the derived protozoan subkingdom Sarcomastigota. Clarifying early eukaryote evolution requires intensive study of properties distinguishing Euglenozoa from neokaryotes and Eozoa from neozoa (eukaryotes except Eozoa; ancestrally defined by haem lyase).

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Section: Where Is the Eukaryotic Root?mentioning

confidence: 61%

Kingdoms Protozoa and Chromista and the eozoan root of the eukaryotic tree

2009

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“…These are the ortholog of Sam50, a member of the Omp85 family, and four β-barrel proteins from the general mitochondrial porin superfamily. One of these is the T. brucei VDAC, functioning as a metabolite transporter (23). A second one is the protein import pore ATOM, whose evolutionary origin is controversial, but shows at least some similarity to the mitochondrial porin family (24,33,34).…”

Section: Discussionmentioning

confidence: 99%

“…Whereas VDAC and Tom40 have so far been found in all eukaryotes, including T. brucei (23,24), MDM10 is specific to the fungal clade.…”

Section: Significancementioning

confidence: 97%

Trypanosomal TAC40 constitutes a novel subclass of mitochondrial β-barrel proteins specialized in mitochondrial genome inheritance

Schnarwiler

Niemann

Doiron

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Mitochondria cannot form de novo but require mechanisms allowing their inheritance to daughter cells. In contrast to most other eukaryotes Trypanosoma brucei has a single mitochondrion whose single-unit genome is physically connected to the flagellum. Here we identify a β-barrel mitochondrial outer membrane protein, termed tripartite attachment complex 40 (TAC40), that localizes to this connection. TAC40 is essential for mitochondrial DNA inheritance and belongs to the mitochondrial porin protein family. However, it is not specifically related to any of the three subclasses of mitochondrial porins represented by the metabolite transporter voltage-dependent anion channel (VDAC), the protein translocator of the outer membrane 40 (TOM40), or the fungi-specific MDM10, a component of the endoplasmic reticulum-mitochondria encounter structure (ERMES). MDM10 and TAC40 mediate cellular architecture and participate in transmembrane complexes that are essential for mitochondrial DNA inheritance. In yeast MDM10, in the context of the ERMES, is postulated to connect the mitochondrial genomes to actin filaments, whereas in trypanosomes TAC40 mediates the linkage of the mitochondrial DNA to the basal body of the flagellum. However, TAC40 does not colocalize with trypanosomal orthologs of ERMES components and, unlike MDM10, it regulates neither mitochondrial morphology nor the assembly of the protein translocase. TAC40 therefore defines a novel subclass of mitochondrial porins that is distinct from VDAC, TOM40, and MDM10. However, whereas the architecture of the TAC40-containing complex in trypanosomes and the MDM10-containing ERMES in yeast is very different, both are organized around a β-barrel protein of the mitochondrial porin family that mediates a DNA-cytoskeleton linkage that is essential for mitochondrial DNA inheritance.organelle | parasitic protozoa

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“…These results clearly indicate that TbPorin is critical for mitochondrial activities thus required for normal cell growth in both forms. Recently, Pusnik et al reported that depletion of the VDAC affects cell growth of the procyclic form only in the absence of glucose (35). Their double-knockout cell lines grew similarly to controls in regular procyclic medium SDM-79.…”

Section: Brucei Vdac Is Critical For Mitochondrial Activity 1421mentioning

confidence: 99%

Downregulation of Mitochondrial Porin Inhibits Cell Growth and Alters Respiratory Phenotype in Trypanosoma brucei

2009

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Porin is the most abundant outer membrane (OM) protein of mitochondria. It forms the aqueous channel on the mitochondrial OM and mediates major metabolite flux between mitochondria and cytosol. Mitochondrial porin in Trypanosoma brucei, a unicellular parasitic protozoan and the causative agent of African trypanosomiasis, possesses a ␤-barrel structure similar to the bacterial OM porin OmpA. T. brucei porin (TbPorin) is present as a monomer as well as an oligomer on the mitochondrial OM, and its expression is developmentally regulated. In spite of its distinct structure, the TbPorin function is similar to those of other eukaryotic porins. TbPorin RNA interference (RNAi) reduced cell growth in both procyclic and bloodstream forms. The depletion of TbPorin decreased ATP production by inhibiting metabolite flux through the OM. Additionally, the level of trypanosome alternative oxidase (TAO) decreased, whereas the levels of cytochromedependent respiratory complexes III and IV increased in TbPorin-depleted mitochondria. Furthermore, the depletion of TbPorin reduced cellular respiration via TAO, which is not coupled with oxidative phosphorylation, but increased the capacity for cyanide-sensitive respiration. Together, these data reveal that TbPorin knockdown reduced the mitochondrial ATP level, which in turn increased the capacity of the cytochromedependent respiratory pathway (CP), in an attempt to compensate for the mitochondrial energy crisis. However, a simultaneous decrease in the substrate-level phosphorylation due to TbPorin RNAi caused growth inhibition in the procyclic form. We also found that the expressions of TAO and CP proteins are coordinately regulated in T. brucei according to mitochondrial energy demand.

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The Single Mitochondrial Porin of Trypanosoma brucei is the Main Metabolite Transporter in the Outer Mitochondrial Membrane

Cited by 97 publications

References 37 publications

Kingdoms Protozoa and Chromista and the eozoan root of the eukaryotic tree

Kingdoms Protozoa and Chromista and the eozoan root of the eukaryotic tree

Trypanosomal TAC40 constitutes a novel subclass of mitochondrial β-barrel proteins specialized in mitochondrial genome inheritance

Downregulation of Mitochondrial Porin Inhibits Cell Growth and Alters Respiratory Phenotype in Trypanosoma brucei

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