Conserved roles of Sam50 and metaxins in VDAC biogenesis

Kozjak-Pavlovic, Vera; Roß, Katharina; Benlasfer, Nouhad; Kimmig, Sonja; Karlas, Alexander; Rudel, Thomas

doi:10.1038/sj.embor.7400982

Cited by 98 publications

(152 citation statements)

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“…Alternatively, as GR is located in the intermembrane space and the matrix (Chew et al, 2003a(Chew et al, , 2003b, it may interact with METAXIN via the import route to the intermembrane space or directly with GR via the intermembrane space exposed domains of METAXIN. A recent study of METAXIN from human cell lines using coimmunoprecipitation revealed that it interacted with an inner membrane protein present in a larger complex with several other proteins (Xie et al, 2007), while another study in humans using BN-PAGE concluded that it was not in a complex with SAM50 (Kozjak-Pavlovic et al, 2007). Thus, the role of METAXIN may differ considerably between species and/or it may play a variety of roles in various organisms.…”

Section: Discussionmentioning

confidence: 99%

“…Arabidopsis METAXIN was identified by sequence similarity to the human METAXIN 1 protein; the latter displays limited sequence similarity to yeast SAM37 and has been implicated in mitochondrial protein import (Armstrong et al, 1997;Abdul et al, 2000). METAXIN1 and METAXIN2 in mammals have been reported to be involved in the import of b-barrel proteins but in a different complex compared with SAM50 (Kozjak-Pavlovic et al, 2007). METAXIN protein has been shown to be present in Arabidopsis mitochondria , but no role in mitochondrial protein import or sorting has been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

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Functional Definition of Outer Membrane Proteins Involved in Preprotein Import into Mitochondria

et al. 2007

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The role of plant mitochondrial outer membrane proteins in the process of preprotein import was investigated, as some of the principal components characterized in yeast have been shown to be absent or evolutionarily distinct in plants. Three outer membrane proteins of Arabidopsis thaliana mitochondria were studied: TOM20 (translocase of the outer mitochondrial membrane), METAXIN, and mtOM64 (outer mitochondrial membrane protein of 64 kD). A single functional Arabidopsis TOM20 gene is sufficient to produce a normal multisubunit translocase of the outer membrane complex. Simultaneous inactivation of two of the three TOM20 genes changed the rate of import for some precursor proteins, revealing limited isoform subfunctionalization. Inactivation of all three TOM20 genes resulted in severely reduced rates of import for some but not all precursor proteins. The outer membrane protein METAXIN was characterized to play a role in the import of mitochondrial precursor proteins and likely plays a role in the assembly of β-barrel proteins into the outer membrane. An outer mitochondrial membrane protein of 64 kD (mtOM64) with high sequence similarity to a chloroplast import receptor was shown to interact with a variety of precursor proteins. All three proteins have domains exposed to the cytosol and interacted with a variety of precursor proteins, as determined by pull-down and yeast two-hybrid interaction assays. Furthermore, inactivation of one resulted in protein abundance changes in the others, suggesting functional redundancy. Thus, it is proposed that all three components directly interact with precursor proteins to participate in early stages of mitochondrial protein import.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Functional Definition of Outer Membrane Proteins Involved in Preprotein Import into Mitochondria

et al. 2007

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“…Mitochondrial isolation and carbonate extraction using 100 mM Na 2 CO 3 , pH 11.5, were performed as described previously (5,11,22). For opening of the OMM, freshly prepared mitochondria were incubated in isotonic (250 mM sucrose, 1 mM EDTA, 10 mM Tris, pH 7.6) or hypotonic (1 mM EDTA, 10 mM Tris, pH 7.6) buffer.…”

Section: Methodsmentioning

confidence: 99%

“…The remaining fraction was centrifuged for 1 h at 100,000 ϫ g, and the supernatant was precipitated with trichloroacetic acid to obtain pure cytosolic fraction. Blue native (BN)-PAGE and Western blotting were performed as described previously (11). Samples for BN-PAGE analysis were solubilized in 1% digitonin buffer (1% digitonin (Sigma) in 20 mM Tris-HCl, 0.1 mM EDTA, 1 mM PMSF, 50 mM NaCl, 10% (v/v) glycerol, pH 7.4).…”

Section: Methodsmentioning

confidence: 99%

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Neisserial Omp85 Protein Is Selectively Recognized and Assembled into Functional Complexes in the Outer Membrane of Human Mitochondria

Kozjak-Pavlovic

Ott

Götz

et al. 2011

Journal of Biological Chemistry

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As a consequence of their bacterial origin, mitochondria contain ␤-barrel proteins in their outer membrane (OMM). These proteins require the translocase of the outer membrane (TOM) complex and the conserved sorting and assembly machinery (SAM) complex for transport and integration into the OMM. The SAM complex and the ␤-barrel assembly machinery (BAM) required for biogenesis of ␤-barrel proteins in bacteria are evolutionarily related. Despite this homology, we show that bacterial ␤-barrel proteins are not universally recognized and integrated into the OMM of human mitochondria. Selectivity exists both at the level of the TOM and the SAM complex. Of all of the proteins we tested, human mitochondria imported only ␤-barrel proteins originating from Neisseria sp., and only Omp85, the central component of the neisserial BAM complex, integrated into the OMM. PorB proteins from different Neisseria, although imported by the TOM, were not recognized by the SAM complex and formed membrane complexes only when functional Omp85 was present at the same time in mitochondria. Omp85 alone was capable of integrating other bacterial ␤-barrel proteins in human mitochondria, but could not substitute for the function of its mitochondrial homolog Sam50. Thus, signals and machineries for transport and assembly of ␤-barrel proteins in bacteria and human mitochondria differ enough to allow only a certain type of ␤-barrel proteins to be targeted and integrated in mitochondrial membranes in human cells.Mitochondria are organelles of bacterial origin, surrounded by an outer (OMM) 4 and an inner membrane (IMM). The OMM contains ␤-barrel proteins, a class of pore-forming proteins additionally found only in chloroplasts and Gram-negative bacteria (1, 2). Similar to the majority of other mitochondrial proteins, ␤-barrel proteins are synthesized in the cytosol and have to be imported into mitochondria with the help of the translocase of the outer mitochondrial membrane (TOM) complex. For the membrane integration and assembly into complexes, ␤-barrel proteins require additional proteinaceous machinery in the OMM. This is so called sorting and assembly machinery (SAM), also known as topogenesis of outer membrane ␤-barrel proteins (TOB complex) (3, 4).The central component of the SAM complex is Sam50/ Tob55, a protein with a function that has been conserved from bacteria to human (4 -6). Other components of the SAM complex include the Sam35/Tob38/Tom38 (7-9) and Sam37/ Mas37/Tom37 (3, 10) proteins in yeast, and Metaxin 1 and Metaxin 2 (11) in mammalian mitochondria.The signals in ␤-barrel proteins that are recognized by the TOM complex belong to internal targeting signals and are not yet fully understood. However, a specific signal has been identified in the C-terminal part of mitochondrial ␤-barrel proteins that directs them to the SAM complex to be properly sorted and integrated into the OMM (12). Unlike in yeast, this signal in mammalian ␤-barrel proteins is always present at the extreme C terminus of the protein, and the addition of even a shor...

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SAMM50 Affects Mitochondrial Morphology through the Association of Drp1 in Mammalian Cells

et al. 2016

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Edited by Barry HalliwellMitochondrial fission and fusion activities are important for cell survival and function. Drp1 is a GTPase protein responsible for mitochondrial division, and SAMM50 is responsible for protein sorting and assembly. We demonstrated that SAMM50 overexpression results in Drp1-dependent mitochondrial fragmentation in HeLa cells. However, the mitochondrial fragmentation induced by SAMM50 overexpression could be reversed through co-expression with MFN2. Furthermore, SAMM50 interacts with Drp1 both in vivo and in vitro. The mitochondria in SAMM50 knockdown HeLa cells displayed a swollen phenotype, and the levels of the SAM complex and OPA1, along with the mitochondrial Drp1 levels, significantly decreased. In addition, mitochondrial inheritance was impaired in SAMM50 silenced cells. These results suggest that SAMM50 affects the Drp1-dependent mitochondrial morphology.

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Conserved roles of Sam50 and metaxins in VDAC biogenesis

Cited by 98 publications

References 25 publications

Functional Definition of Outer Membrane Proteins Involved in Preprotein Import into Mitochondria

Functional Definition of Outer Membrane Proteins Involved in Preprotein Import into Mitochondria

Neisserial Omp85 Protein Is Selectively Recognized and Assembled into Functional Complexes in the Outer Membrane of Human Mitochondria

SAMM50 Affects Mitochondrial Morphology through the Association of Drp1 in Mammalian Cells

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