Shy1p occurs in a high molecular weight complex and is required for efficient assembly of cytochrome <i>c</i> oxidase in yeast

Nijtmans, Leo; Artal‐Sanz, Marta; Bučko, Marek; Farhoud, Murtada H; Feenstra, Marike; Hakkaart, G.A.J.; Zeviani, Massimo; Grivell, Leslie A.

doi:10.1016/s0014-5793(01)02447-4

Cited by 69 publications

(63 citation statements)

References 33 publications

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“…We find a slightly but significantly reduced oxygen consumption rate in phb(RNAi)-treated worms compared with control worms. In addition, we show that PHB protein contents are elevated in situations of altered mitochondrial metabolism, such as when imbalances in respiratory enzyme subunits occur, as has been reported in other systems (6,17,18). In strong contrast to the yeast situation, we report a severe loss of function phenotype for depletion of the mitochondrial PHB complex during organismal development.…”

supporting

confidence: 74%

“…PHB mRNA levels are induced in yeast cells at the diauxic shift, when cells switch from nonoxidative to oxidative growth (38). Similarly, expression levels of PHB proteins increase in yeast mutants where imbalances between nuclear and mitochondrially encoded subunits occur (6,17). Inhibition of mitochondrial protein synthesis also leads to imbalances between mitochondrial and nuclear-encoded gene products (39).…”

Section: Discussionmentioning

confidence: 99%

“…Induction of PHB Proteins upon Mitochondrial Stress-PHB protein expression increases when there is an imbalance in the synthesis of mitochondrial respiratory chain enzyme subunits in yeast (6,17) and in human cells (18).…”

Section: Phb(rnai) Animals Show Increased Sensitivity To Oxidativementioning

confidence: 99%

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The Mitochondrial Prohibitin Complex Is Essential for Embryonic Viability and Germline Function in Caenorhabditis elegans

Artal‐Sanz

Tsang

Willems

et al. 2003

Journal of Biological Chemistry

189

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Prohibitins in eukaryotes consist of two subunits (PHB1 and PHB2) that together form a high molecular weight complex in the mitochondrial inner membrane. The evolutionary conservation and the ubiquitous expression in mammalian tissues of the prohibitin complex suggest an important function among eukaryotes. The PHB complex has been shown to play a role in the stabilization of newly synthesized subunits of mitochondrial respiratory enzymes in the yeast Saccharomyces cerevisiae. We have used Caenorhabditis elegans as model system to study the role of the PHB complex during development of a multicellular organism. We demonstrate that prohibitins in C. elegans form a high molecular weight complex in the mitochondrial inner membrane similar to that of yeast and humans. By using RNA-mediated gene inactivation, we show that PHB proteins are essential during embryonic development and are required for somatic and germline differentiation in the larval gonad. We further demonstrate that a deficiency in PHB proteins results in altered mitochondrial biogenesis in body wall muscle cells. This paper reports a strong loss of function phenotype for prohibitin gene inactivation in a multicellular organism and shows for the first time that prohibitins serve an essential role in mitochondrial function during organismal development.Prohibitins (Phb1p and Phb2p), referred to here as PHB proteins, are evolutionarily strongly conserved proteins that are located in mitochondria in yeast, plants, and mammals (1-6). In mammalian and yeast cells, it has been demonstrated that PHB proteins associate with each other to form a high molecular weight complex (the PHB complex) in the mitochondrial inner membrane (5, 6). Although diverse cellular functions have been attributed to both PHB proteins (see Ref. 7 for a review), such as a role in cell cycle regulation (8 -11) and in cell surface signaling (12, 13), these functions are difficult to reconcile with the exclusive localization of mammalian PHB proteins to mitochondria (1, 3). To date, studies on the yeast PHB complex have provided convincing evidence for a direct role in mitochondrial function. The PHB complex has been found to co-purify with the m-AAA (matrix-ATPase associated with a variety of cellular activities) protease, and a role as a negative regulator of the protease has been proposed (5). Yeast PHB proteins are capable of stabilizing newly synthesized mitochondrially encoded proteins through direct interaction, suggesting a role in mitochondrial respiratory complex assembly (5, 6). We have suggested a role for PHB proteins in the biogenesis of mitochondria as a holdase/unfoldase type of protein specifically required in situations of metabolic stress (6). Based on structural data from chemical cross-linking and mass spectrometry, we predict a barrel-like structure for the yeast PHB complex, in the cavity of which mitochondrial products might be held (14).At the phenotypic level, disruption of PHB genes in yeast results in a shortening of the replicative life span due to premature...

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supporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

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The Mitochondrial Prohibitin Complex Is Essential for Embryonic Viability and Germline Function in Caenorhabditis elegans

Artal‐Sanz

Tsang

Willems

et al. 2003

Journal of Biological Chemistry

189

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“…Synthesis of COX2 and COX3 and their stability over a 7-h chase were as in wild-type cells. Although these subunits have a longer half-life than COX1, they are known to be unstable when COX assembly is compromised (26,35), and, accordingly, their steady-state levels in hCOA3 interfered cells were lowered markedly.…”

Section: Discussionmentioning

confidence: 99%

hCOA3 Stabilizes Cytochrome c Oxidase 1 (COX1) and Promotes Cytochrome c Oxidase Assembly in Human Mitochondria

Clemente

Peralta

Cruz-Bermúdez

et al. 2013

Journal of Biological Chemistry

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Background: Assembly of cytochrome c oxidase (COX), complex IV of the respiratory chain, requires a great number of accessory proteins known as assembly factors. Results: hCOA3 interacts with newly synthesized COX1 and promotes its assembly with subsequent COX subunits. Conclusion: hCOA3 participates in COX biogenesis in humans. Significance: hCOA3 is a new candidate gene to screen in patients with COX deficiency.

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“…COX is the terminal enzyme in both the eukaryotic and prokaryotic respiratory chain, catalyzing the reduction of molecular oxygen to water with concomitant proton pumping from the matrix to the intermembrane space. Studies in Surf1ÿ/ÿ cells from humans (Tiranti et al 1999a), mice (Agostino et al 2003), and yeast (Nijtmans et al 2001) indicate that SURF1 is involved in COX assembly. However, in human Surf1ÿ/ÿ cells low amounts of apparently fully assembled COX can still be detected by 2D-blue native electrophoresis, suggesting redundancy of the SURF1 function via unknown mechanism(s) (Coenen et al 1999;Tiranti et al 1999a;Hanson et al 2001).…”

mentioning

confidence: 99%

Post-transcriptional Silencing and Functional Characterization of theDrosophila melanogasterHomolog of HumanSurf1

Zordan¹,

Cisotto²,

Benna³

et al. 2006

Genetics

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Mutations in Surf1, a human gene involved in the assembly of cytochrome c oxidase (COX), cause Leigh syndrome, the most common infantile mitochondrial encephalopathy, characterized by a specific COX deficiency. We report the generation and characterization of functional knockdown (KD) lines for Surf1 in Drosophila. KD was produced by post-transcriptional silencing employing a transgene encoding a dsRNA fragment of the Drosophila homolog of human Surf1, activated by the UAS transcriptional activator. Two alternative drivers, Actin5C-GAL4 or elav-GAL4, were used to induce silencing ubiquitously or in the CNS, respectively. Actin5C-GAL4 KD produced 100% egg-to-adult lethality. Most individuals died as larvae, which were sluggish and small. The few larvae reaching the pupal stage died as early imagos. Electron microscopy of larval muscles showed severely altered mitochondria. elav-GAL4-driven KD individuals developed to adulthood, although cephalic sections revealed low COX-specific activity. Behavioral and electrophysiological abnormalities were detected, including reduced photoresponsiveness in KD larvae using either driver, reduced locomotor speed in Actin5C-GAL4 KD larvae, and impaired optomotor response as well as abnormal electroretinograms in elav-GAL4 KD flies. These results indicate important functions for SURF1 specifically related to COX activity and suggest a crucial role of mitochondrial energy pathways in organogenesis and CNS development and function.

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Shy1p occurs in a high molecular weight complex and is required for efficient assembly of cytochrome c oxidase in yeast

Cited by 69 publications

References 33 publications

The Mitochondrial Prohibitin Complex Is Essential for Embryonic Viability and Germline Function in Caenorhabditis elegans

The Mitochondrial Prohibitin Complex Is Essential for Embryonic Viability and Germline Function in Caenorhabditis elegans

hCOA3 Stabilizes Cytochrome c Oxidase 1 (COX1) and Promotes Cytochrome c Oxidase Assembly in Human Mitochondria

Post-transcriptional Silencing and Functional Characterization of theDrosophila melanogasterHomolog of HumanSurf1

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