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

2005 ◽  
Vol 16 (11) ◽  
pp. 5202-5214 ◽  
Author(s):  
Katrin Brandner ◽  
David U. Mick ◽  
Ann E. Frazier ◽  
Rebecca D. Taylor ◽  
Chris Meisinger ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Respiratory Chain ◽  
Mitochondrial Membrane ◽  
Barth Syndrome ◽  
Outer Mitochondrial Membrane ◽  
Respiratory Chain Complexes ◽  
Complex Iv ◽  
Inner Membrane ◽  
Chain Complexes ◽  
Mitochondrial Membrane Protein

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 taz1Δ mitochondria and show that these are destabilized in taz1Δ mitochondria. This leads to a selective release of a complex IV monomer from the III2IV2 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 taz1Δ mitochondria. We conclude that inactivation of Taz1 affects both assembly and stability of respiratory chain complexes in the inner membrane of mitochondria.

scholarly journals Selective and Reversible Disruption of Mitochondrial Inner Membrane Protein Complexes by Lipophilic Cations

2021 ◽  
Author(s):  
Anezka Kafkova ◽  
Lisa Tilokani ◽  
Filip Trčka ◽  
Veronika Šrámková ◽  
Marie Vancová ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Respiratory Chain ◽  
Mitochondrial Membrane ◽  
Mitochondrial Morphology ◽  
Respiratory Chain Complexes ◽  
Inner Membrane ◽  
Protein Levels ◽  
Mitochondrial Inner Membrane ◽  
Chain Complexes ◽  
The Impact

ABSTRACTMitochondria represent an attractive drug target in the treatment of many diseases. One of the most commonly used approaches to deliver therapeutics specifically into mitochondria is their conjugation to the triphenylphosphonium (TPP) moiety. While the TPP molecule is often regarded as biologically inert, there is evidence that the moiety itself has a significant impact on the activity of mitochondrial respiratory chain complexes.We studied the impact of a subchronic exposure of C2C12 mouse myoblasts to a set of TPP derivatives. Our results show that the alkyl-TPP cause dose- and hydrophobicity-dependent alterations of mitochondrial morphology and a selective decrease in the amounts of mitochondrial inner membrane (but not outer membrane) proteins including structural subunits of the respiratory chain complexes (such as MT-CO1 of complex IV or NDUFB8 of complex I), as well as components of the mitochondrial calcium uniporter complex (MCUC). The treatment with alkyl-TPP additionally resulted in OPA1-cleavage. Both the structural and functional effects of alkyl-TPP were found to be reversible. A similar effect was observed with the mitochondria-targeted antioxidant MitoQ. We further show that this effect on protein levels cannot be explained solely by a decrease in mitochondrial membrane potential.We conclude that TPP derivatives negatively affect mitochondrial structure and function at least in part through their effect on selective mitochondrial membrane protein levels via a reversible controlled process.

scholarly journals Genetic analysis of dTSPO , an outer mitochondrial membrane protein, reveals its functions in apoptosis, longevity, and Aβ42‐induced neurodegeneration

Aging Cell ◽  
2014 ◽  
Vol 13 (3) ◽  
pp. 507-518 ◽  
Author(s):  
Ran Lin ◽  
Alessia Angelin ◽  
Federico Da Settimo ◽  
Claudia Martini ◽  
Sabrina Taliani ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Genetic Analysis ◽  
Mitochondrial Membrane ◽  
Outer Mitochondrial Membrane ◽  
Mitochondrial Membrane Protein

scholarly journals Respiratory chain supercomplexes associate with the cysteine desulfurase complex of the iron–sulfur cluster assembly machinery

2018 ◽  
Vol 29 (7) ◽  
pp. 776-785 ◽  
Author(s):  
Lena Böttinger ◽  
Christoph U. Mårtensson ◽  
Jiyao Song ◽  
Nicole Zufall ◽  
Nils Wiedemann ◽  
...  
Keyword(s):  
Respiratory Chain ◽  
Complex Iii ◽  
Bc1 Complex ◽  
Cytochrome Bc1 Complex ◽  
Respiratory Chain Complexes ◽  
Cysteine Desulfurase ◽  
Complex Iv ◽  
Iron Sulfur Cluster ◽  
Iron Sulfur ◽  
Chain Complexes

Mitochondria are the powerhouses of eukaryotic cells. The activity of the respiratory chain complexes generates a proton gradient across the inner membrane, which is used by the F1FO-ATP synthase to produce ATP for cellular metabolism. In baker’s yeast, Saccharomyces cerevisiae, the cytochrome bc1 complex (complex III) and cytochrome c oxidase (complex IV) associate in respiratory chain supercomplexes. Iron–sulfur clusters (ISC) form reactive centers of respiratory chain complexes. The assembly of ISC occurs in the mitochondrial matrix and is essential for cell viability. The cysteine desulfurase Nfs1 provides sulfur for ISC assembly and forms with partner proteins the ISC-biogenesis desulfurase complex (ISD complex). Here, we report an unexpected interaction of the active ISD complex with the cytochrome bc1 complex and cytochrome c oxidase. The individual deletion of complex III or complex IV blocks the association of the ISD complex with respiratory chain components. We conclude that the ISD complex binds selectively to respiratory chain supercomplexes. We propose that this molecular link contributes to coordination of iron–sulfur cluster formation with respiratory activity.

scholarly journals The Outer Mitochondrial Membrane Protein mitoNEET Contains a Novel Redox-active 2Fe-2S Cluster

2007 ◽  
Vol 282 (33) ◽  
pp. 23745-23749 ◽  
Author(s):  
Sandra E. Wiley ◽  
Mark L. Paddock ◽  
Edward C. Abresch ◽  
Larry Gross ◽  
Peter van der Geer ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Mitochondrial Membrane ◽  
Outer Mitochondrial Membrane ◽  
Redox Active ◽  
Mitochondrial Membrane Protein

scholarly journals Expanding the Range of Redox Potentials of the 2Fe-2S Clusters of the Outer Mitochondrial Membrane Protein MitoNEET

2010 ◽  
Vol 98 (3) ◽  
pp. 235a
Author(s):  
John A. Zuris ◽  
Mark L. Paddock ◽  
Andrea R. Conlan ◽  
Edward C. Abresch ◽  
Rachel Nechushtai ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Mitochondrial Membrane ◽  
Outer Mitochondrial Membrane ◽  
Redox Potentials ◽  
Mitochondrial Membrane Protein

scholarly journals Structural Basis for Phosphate Stabilization of the Uniquely Coordinated 2Fe-2S Cluster of the Outer Mitochondrial Membrane Protein MitoNEET.∗

2009 ◽  
Vol 96 (3) ◽  
pp. 442a-443a ◽  
Author(s):  
Christina Homer ◽  
David Yee ◽  
Herbert L. Axelrod ◽  
Aina E. Cohen ◽  
Edward C. Abresch ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Mitochondrial Membrane ◽  
Structural Basis ◽  
Outer Mitochondrial Membrane ◽  
Mitochondrial Membrane Protein

scholarly journals Effect of inhibitors of mitochondrial respiratory chain complexes on the electromechanical activity in human myocardium

Medicina ◽  
2010 ◽  
Vol 46 (10) ◽  
pp. 679
Author(s):  
Vida Gendvilienė ◽  
Irma Martišienė ◽  
Danguolė Zablockaitė ◽  
Jonas Jurevičius
Keyword(s):  
Respiratory Chain ◽  
Control Level ◽  
Chain Complex ◽  
Mitochondrial Respiratory Chain ◽  
Human Myocardium ◽  
Contraction Force ◽  
Respiratory Chain Complexes ◽  
Complex Iv ◽  
Resting Tension ◽  
Chain Complexes

The aim of the study was to investigate the effect of inhibitors of mitochondrial respiratory chain complexes I, III, and IV on the electromechanical activity in human myocardium. Material and methods. The experiments were performed on the human myocardial strips obtained from patients with heart failure (NYHA class III or IV) using a conventional method of registration of myocardial electromechanical activity. Under the perfusion with physiological Tyrode solution (control), contraction force (P) was 0.94±0.12 mN (n=16), relaxation time (t50) was 173.38±5.03 ms (n=15), action potential durations measured at 50% (AP50) and 90% (AP90) repolarization were 248.96±13.38 ms and 398.59±17.93 ms, respectively (n=13). Results. The inhibition of respiratory chain complex I by rotenone (3×10–5 M, the highest concentration applied) decreased contraction force of human myocardium to 48.99%±14.74% (n=3) (P<0.05); AP50, to 81.34%±15.81%; and AP90, to 87.28%±7.25% (n=3) (P>0.05) of control level, while relaxation time and resting tension remained almost unchanged. Antimycin A, an inhibitor of complex III, applied at the highest concentration (3×10–4 M) reduced P to 41.66%±8.8% (n=5) (P<0.001) and marginally increased t50 and decreased the durations of AP. Anoxia (3 mM Na2S2O4) that inhibits the activity of complex IV reduced the contraction force to 9.23%±3.56% (n=6) (P<0.001), AP50 and AP90 to 65.46%±9.95% and 71.07%±8.39% (n=5) (P<0.05) of control level, respectively; furthermore, the resting tension augmented (contracture developed). Conclusions. Our results show that the inhibition of respiratory chain complex IV had the strongest inhibitory effect on the electromechanical activity of failing human myocardium.

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