New Developments in Mitochondrial Assembly

Koehler, Carla M.

doi:10.1146/annurev.cellbio.20.010403.105057

Cited by 273 publications

(262 citation statements)

References 151 publications

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“…Dissociation of the membrane potential (⌬ ) before import by the addition of the K ϩ -ionophore valinomycin in the presence of K ϩ in the buffer did not affect transport of the precursor to a protease-protected location ( Figure 1B, lane 6). Because protein transport across the inner mitochondrial membrane depends on ⌬ (Neupert, 1997;Jensen and Dunn, 2002;Koehler, 2004;Rehling et al, 2004), we concluded that Taz1 was not transported across the inner membrane.…”

Section: Import Of Taz1 Into S Cerevisiae Mitochondriamentioning

confidence: 89%

Taz1, an Outer Mitochondrial Membrane Protein, Affects Stability and Assembly of Inner Membrane Protein Complexes: Implications for Barth Syndrome

Brandner

Mick

Frazier

et al. 2005

MBoC

190

150

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The Saccharomyces cerevisiae Taz1 protein is the orthologue of human Tafazzin, a protein that when inactive causes Barth Syndrome (BTHS), a severe inherited X-linked disease. Taz1 is a mitochondrial acyltransferase involved in the remodeling of cardiolipin. We show that Taz1 is an outer mitochondrial membrane protein exposed to the intermembrane space (IMS). Transport of Taz1 into mitochondria depends on the receptor Tom5 of the translocase of the outer membrane (TOM complex) and the small Tim proteins of the IMS, but is independent of the sorting and assembly complex (SAM). TAZ1 deletion in yeast leads to growth defects on nonfermentable carbon sources, indicative of a defect in respiration. Because cardiolipin has been proposed to stabilize supercomplexes of the respiratory chain complexes III and IV, we assess supercomplexes in taz1⌬ mitochondria and show that these are destabilized in taz1⌬ mitochondria. This leads to a selective release of a complex IV monomer from the III 2 IV 2 supercomplex. In addition, assembly analyses of newly imported subunits into complex IV show that incorporation of the complex IV monomer into supercomplexes is affected in taz1⌬ mitochondria. We conclude that inactivation of Taz1 affects both assembly and stability of respiratory chain complexes in the inner membrane of mitochondria. INTRODUCTIONBarth Syndrome is an X-linked recessive disorder that is characterized by cardioskeletal myopathy, neutropenia, increased urine levels of 3-methylglutaconic acid, abnormal mitochondria, and respiratory chain dysfunction (Barth et al., 1983(Barth et al., , 1996Kelley et al., 1991;D'Adamo et al., 1997). The disease is often fatal in infancy and early childhood because of cardiac failure and bacterial infections (Barth et al., 2004). Bione et al. (1996) identified the gene responsible, termed Tafazzin (TAZ), and localized it to region q28 on the X chromosome. Sequence analyses demonstrate that the Taz protein is highly conserved from yeast to man and that it displays sequence similarity to acyltransferases that participate in the metabolism of phospholipids (Neuwald, 1997). Phospholipid analyses of fibroblasts from patients and yeast taz1⌬ mutant cells show reduced cardiolipin levels and an altered acyl chain composition (Vreken et al., 2000;Vaz et al., 2003;Xu et al., 2003;Gu et al., 2004).Cardiolipin is formed by two glycerol-linked phosphatidyl moieties. The four acyl side chains are usually monoand di-unsaturated fatty acids in higher eukaryotes. Remodeling of cardiolipin through a cycle of deacylation and successive reacylation leads to the final and specific acyl composition. In heart and skeletal muscle mitochondria the tetralinoleoyl species predominates Xu et al., 2003;Hatch, 2004). Cardiolipin is primarily found in the mitochondrial membranes of eukaryotes (Hoch, 1992) and the bacterial cytoplasmic membrane. Although the molecular function of cardiolipin is still unclear, several studies have suggested that it is required for the proper function of some proteins and protein complexe...

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Section: Import Of Taz1 Into S Cerevisiae Mitochondriamentioning

confidence: 89%

Taz1, an Outer Mitochondrial Membrane Protein, Affects Stability and Assembly of Inner Membrane Protein Complexes: Implications for Barth Syndrome

Brandner

Mick

Frazier

et al. 2005

MBoC

190

150

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“…Recent work by Youle, Jensen, Koehler, Scorrano and others has revealed a role for mitochondrial shape in apoptosis. [74][75][76][77][78] In particular, mitochondria typically fragment during apoptosis and inhibition of fission blocks cell death. Are the fission and fusion proteins Drp1, Opa1 or endophilin B candidates for Bax partners?…”

Section: Future Perspectivesmentioning

confidence: 99%

Is MAC the knife that cuts cytochrome c from mitochondria during apoptosis?

2006

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Apoptosis is a phenomenon fundamental to higher eukaryotes and essential to mechanisms controlling tissue homeostasis. Bcl-2 family proteins tightly control this cell death program by regulating the permeabilization of the mitochondrial outer membrane and, hence, the release of cytochrome c and other proapoptotic factors. Mitochondrial apoptosisinduced channel (MAC) is the mitochondrial apoptosisinduced channel and is responsible for cytochrome c release early in apoptosis. MAC activity is detected by patch clamping mitochondria at the time of cytochrome c release. The Bcl-2 family proteins regulate apoptosis by controlling the formation of MAC. Depending on cell type and apoptotic inducer, Bax and/or Bak are structural component(s) of MAC. Overexpression of the antiapoptotic protein Bcl-2 eliminates MAC activity. The focus of this review is a biophysical characterization of MAC activity and its regulation by Bcl-2 family proteins, and ends with some discussion of therapeutic targets.

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“…Tom20 is thought to be responsible for the import of preproteins bearing classical matrix-directed N-terminal signal sequences, or leader peptides. Tom70, the alternate receptor, is thought to mediate the import of preproteins that contain targeting information within their mature sequences (Koehler, 2004;Rehling et al, 2004). Although much of our knowledge of import derives from work in Saccharomyces cerevisiae and Neurospora crassa, the biological functions of the human Tom70 and Tom20 receptors seem to be largely conserved (Iwahashi et al, 1997;Schleiff et al, 1997;Yano et al, 1997;Suzuki et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Multiple 40-kDa Heat-Shock Protein Chaperones Function in Tom70-dependent Mitochondrial Import

Bhangoo

Tzankov

Fan

et al. 2007

MBoC

108

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Mitochondrial preproteins that are imported via the translocase of the mitochondrial outer membrane (Tom)70 receptor are complexed with cytosolic chaperones before targeting to the mitochondrial outer membrane. The adenine nucleotide transporter (ANT) follows this pathway, and its purified mature form is identical to the preprotein. Purified ANT was reconstituted with chaperones in reticulocyte lysate, and bound proteins were identified by mass spectrometry. In addition to 70-kDa heat-shock cognate protein (Hsc70) and 90-kDa heat-shock protein (Hsp90), a specific subset of cochaperones were found, but no mitochondria-specific targeting factors were found. Interestingly, three different Hsp40-related J-domain proteins were identified: DJA1, DJA2, and DJA4. The DJAs bound preproteins to different extents through their C-terminal regions. DJA dominant-negative mutants lacking the N-terminal J-domains impaired mitochondrial import. The mutants blocked the binding of Hsc70 to preprotein, but with varying efficiency. The DJAs also showed significant differences in activation of the Hsc70 ATPase and Hsc70-dependent protein refolding. In HeLa cells, the DJAs increased new protein folding and mitochondrial import, although to different extents. No single DJA was superior to the others in all aspects, but each had a profile of partial specialization. The Hsp90 cochaperones p23 and Aha1 also regulated Hsp90 -preprotein interactions. We suggest that multiple cochaperones with similar yet partially specialized properties cooperate in optimal chaperone-preprotein complexes.

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New Developments in Mitochondrial Assembly

Cited by 273 publications

References 151 publications

Taz1, an Outer Mitochondrial Membrane Protein, Affects Stability and Assembly of Inner Membrane Protein Complexes: Implications for Barth Syndrome

Taz1, an Outer Mitochondrial Membrane Protein, Affects Stability and Assembly of Inner Membrane Protein Complexes: Implications for Barth Syndrome

Is MAC the knife that cuts cytochrome c from mitochondria during apoptosis?

Multiple 40-kDa Heat-Shock Protein Chaperones Function in Tom70-dependent Mitochondrial Import

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