Fmp30, Mdm31, and Mdm32 Function in Ups1-Independent Cardiolipin Accumulation Under Low Phosphatidylethanolamine Conditions

Membrane Proteins ◽

Phosphatidic Acid ◽

Inner Membrane ◽

Per Se

Maintenance of the cardiolipin (CL) level largely depends on Ups1-Mdm35 complex-mediated intramitochondrial phosphatidic acid transfer. In addition, the presence of an alternative CL accumulation pathway has been suggested in the yeast Saccharomyces cerevisiae. This pathway is independent of the Ups1-Mdm35 complex and stimulated by loss of Ups2, which forms a complex with Mdm35 and mediates intramitochondrial transfer of phosphatidylserine for phosphatidylethanolamine synthesis. Recently, we found that the alternative CL accumulation pathway is enhanced by a lowered phosphatidylethanolamine level, not by loss of Ups2 per se, and depends on three mitochondrial inner membrane proteins, Fmp30, Mdm31, and Mdm32.

A Genomewide Screen for Petite-negative Yeast Strains Yields a New Subunit of the i-AAA Protease Complex

Molecular Biology of the Cell ◽

10.1091/mbc.e05-06-0585 ◽

2006 ◽

Vol 17 (1) ◽

pp. 213-226 ◽

Cited By ~ 58

Author(s):

Cory D. Dunn ◽

Marina S. Lee ◽

Forrest A. Spencer ◽

Robert E. Jensen

Keyword(s):

Mitochondrial Dna ◽

Cell Viability ◽

Inner Membrane ◽

Yeast Strains ◽

Petite Negative Yeast ◽

Yeast Mutants ◽

The Relationship

Unlike many other organisms, the yeast Saccharomyces cerevisiae can tolerate the loss of mitochondrial DNA (mtDNA). Although a few proteins have been identified that are required for yeast cell viability without mtDNA, the mechanism of mtDNA-independent growth is not completely understood. To probe the relationship between the mitochondrial genome and cell viability, we conducted a microarray-based, genomewide screen for mitochondrial DNA-dependent yeast mutants. Among the several genes that we discovered is MGR1, which encodes a novel subunit of the i-AAA protease complex located in the mitochondrial inner membrane. mgr1Δ mutants retain some i-AAA protease activity, yet mitochondria lacking Mgr1p contain a misassembled i-AAA protease and are defective for turnover of mitochondrial inner membrane proteins. Our results highlight the importance of the i-AAA complex and proteolysis at the inner membrane in cells lacking mitochondrial DNA.

Mdj2p, a novel DnaJ homolog in the mitochondrial inner membrane of the yeast Saccharomyces cerevisiae

Journal of Molecular Biology ◽

10.1006/jmbi.1997.1267 ◽

1997 ◽

Vol 272 (4) ◽

pp. 477-483 ◽

Cited By ~ 37

Author(s):

Benedikt Westermann ◽

Walter Neupert

Keyword(s):

Inner Membrane ◽

Mitochondrial Inner Membrane

Phosphatidic acid biosynthesis in the model organism yeast Saccharomyces cerevisiae - a survey

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids ◽

10.1016/j.bbalip.2021.158907 ◽

2021 ◽

pp. 158907

Author(s):

Karin Athenstaedt

Keyword(s):

Phosphatidic Acid ◽

Model Organism ◽

Acid Biosynthesis ◽

Yeast Saccharomyces Cerevisiae

Prohibitins Regulate Membrane Protein Degradation by the m-AAA Protease in Mitochondria

Molecular and Cellular Biology ◽

10.1128/mcb.19.5.3435 ◽

1999 ◽

Vol 19 (5) ◽

pp. 3435-3442 ◽

Cited By ~ 208

Author(s):

Gregor Steglich ◽

Walter Neupert ◽

Thomas Langer

Keyword(s):

Cell Growth ◽

Membrane Proteins ◽

Eukaryotic Cells ◽

Mitochondrial Morphology ◽

Regulatory Effect ◽

Inner Membrane ◽

Functional Activities ◽

Native Molecular Mass ◽

Affect Cell Growth

ABSTRACT Prohibitins comprise a protein family in eukaryotic cells with potential roles in senescence and tumor suppression. Phb1p and Phb2p, members of the prohibitin family in Saccharomyces cerevisiae, have been implicated in the regulation of the replicative life span of the cells and in the maintenance of mitochondrial morphology. The functional activities of these proteins, however, have not been elucidated. We demonstrate here that prohibitins regulate the turnover of membrane proteins by the m-AAA protease, a conserved ATP-dependent protease in the inner membrane of mitochondria. The m-AAA protease is composed of the homologous subunits Yta10p (Afg3p) and Yta12p (Rca1p). Deletion ofPHB1 or PHB2 impairs growth of Δyta10 or Δyta12 cells but does not affect cell growth in the presence of the m-AAA protease. A prohibitin complex with a native molecular mass of approximately 2 MDa containing Phb1p and Phb2p forms a supercomplex with them-AAA protease. Proteolysis of nonassembled inner membrane proteins by the m-AAA protease is accelerated in mitochondria lacking Phb1p or Phb2p, indicating a negative regulatory effect of prohibitins on m-AAA protease activity. These results functionally link members of two conserved protein families in eukaryotes to the degradation of membrane proteins in mitochondria.

Daughter cells of Saccharomyces cerevisiae from old mothers display a reduced life span.

The Journal of Cell Biology ◽

10.1083/jcb.127.6.1985 ◽

1994 ◽

Vol 127 (6) ◽

pp. 1985-1993 ◽

Cited By ~ 215

Author(s):

B K Kennedy ◽

N R Austriaco ◽

L Guarente

Keyword(s):

Life Span ◽

Daughter Cell ◽

Young Mothers ◽

Young Mother ◽

Daughter Cells ◽

Per Se ◽

Mother Cells ◽

Maximum Occurrence

The yeast Saccharomyces cerevisiae typically divides asymmetrically to give a large mother cell and a smaller daughter cell. As mother cells become old, they enlarge and produce daughter cells that are larger than daughters derived from young mother cells. We found that occasional daughter cells were indistinguishable in size from their mothers, giving rise to a symmetric division. The frequency of symmetric divisions became greater as mother cells aged and reached a maximum occurrence of 30% in mothers undergoing their last cell division. Symmetric divisions occurred similarly in rad9 and ste12 mutants. Strikingly, daughters from old mothers, whether they arose from symmetric divisions or not, displayed reduced life spans relative to daughters from young mothers. Because daughters from old mothers were larger than daughters from young mothers, we investigated whether an increased size per se shortened life span and found that it did not. These findings are consistent with a model for aging that invokes a senescence substance which accumulates in old mother cells and is inherited by their daughters.

Role of positively charged transmembrane segments in the insertion and assembly of mitochondrial inner-membrane proteins

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.251503098 ◽

2001 ◽

Vol 98 (24) ◽

pp. 13814-13819 ◽

Cited By ~ 19

Author(s):

Y. Saint-Georges ◽

P. Hamel ◽

C. Lemaire ◽

G. Dujardin

Keyword(s):

Membrane Proteins ◽

Inner Membrane ◽

Transmembrane Segments ◽

Positively Charged

Translocation of mitochondrial inner-membrane proteins: conformation matters

Trends in Biochemical Sciences ◽

10.1016/j.tibs.2006.03.006 ◽

2006 ◽

Vol 31 (5) ◽

pp. 259-267 ◽

Cited By ~ 27

Author(s):

Carine de Marcos-Lousa ◽

Dionisia P Sideris ◽

Kostas Tokatlidis

Keyword(s):

Membrane Proteins ◽

Inner Membrane ◽

Mitochondrial Inner Membrane

The J-related Segment of Tim44 Is Essential for Cell Viability: A Mutant Tim44 Remains in the Mitochondrial Import Site, but Inefficiently Recruits mtHsp70 and Impairs Protein Translocation

The Journal of Cell Biology ◽

10.1083/jcb.145.5.961 ◽

1999 ◽

Vol 145 (5) ◽

pp. 961-972 ◽

Cited By ~ 36

Author(s):

Alessio Merlin ◽

Wolfgang Voos ◽

Ammy C. Maarse ◽

Michiel Meijer ◽

Nikolaus Pfanner ◽

...

Keyword(s):

Protein Import ◽

Protein Translocation ◽

Adaptor Protein ◽

Dependent Manner ◽

Wild Type ◽

Inner Membrane ◽

J Proteins

Tim44 is a protein of the mitochondrial inner membrane and serves as an adaptor protein for mtHsp70 that drives the import of preproteins in an ATP-dependent manner. In this study we have modified the interaction of Tim44 with mtHsp70 and characterized the consequences for protein translocation. By deletion of an 18-residue segment of Tim44 with limited similarity to J-proteins, the binding of Tim44 to mtHsp70 was weakened. We found that in the yeast Saccharomyces cerevisiae the deletion of this segment is lethal. To investigate the role of the 18-residue segment, we expressed Tim44Δ18 in addition to the endogenous wild-type Tim44. Tim44Δ18 is correctly targeted to mitochondria and assembles in the inner membrane import site. The coexpression of Tim44Δ18 together with wild-type Tim44, however, does not stimulate protein import, but reduces its efficiency. In particular, the promotion of unfolding of preproteins during translocation is inhibited. mtHsp70 is still able to bind to Tim44Δ18 in an ATP-regulated manner, but the efficiency of interaction is reduced. These results suggest that the J-related segment of Tim44 is needed for productive interaction with mtHsp70. The efficient cooperation of mtHsp70 with Tim44 facilitates the translocation of loosely folded preproteins and plays a crucial role in the import of preproteins which contain a tightly folded domain.