Manuel Rojo

Manuel Rojo
CNRS & Université de Bordeaux · Institut de Biochimie et Génétique Cellulaires (IBGC)

PhD

About

49
Publications
5,489
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
4,578
Citations
Additional affiliations
January 1999 - January 2008
Sorbonne Université
Position
  • Senior Researcher
January 1994 - January 1999
University of Geneva
Position
  • Researcher

Publications

Publications (49)
Article
Mitochondrial ATP-synthesis is catalyzed by a F1Fo-ATP synthase, an enzyme of dual genetic origin enriched at the edge of cristae where it plays a key role in their structure/stability. The enzyme’s biogenesis remains poorly understood, both from a mechanistic and a compartmentalization point of view. The present study provides novel molecular insi...
Preprint
Full-text available
Mitochondrial ATP-synthesis is catalyzed by F1Fo-ATP synthase, an enzyme of dual genetic origin. TMEM70, a transmembrane protein mutated in neonatal encephalo-cardiomyopathies, is required for assembly/stability of ATP-synthase, but its precise role remains largely unknown. Herein, we demonstrate a role of TMEM70 in the formation of the c-ring (an...
Article
Full-text available
Charcot-Marie-Tooth disease type 2A (CMT2A) is caused by dominant alleles of the mitochondrial pro-fusion factor Mitofusin 2 (MFN2). To address the consequences of these mutations on mitofusin activity and neuronal function, we generate Drosophila models expressing in neurons the two most frequent substitutions (R94Q and R364W, the latter never stu...
Article
Mitochondria are double-membrane-bound organelles that constantly change shape through membrane fusion and fission. Outer mitochondrial membrane fusion is controlled by Mitofusin, whose molecular architecture consists of an N-terminal GTPase domain, a first heptad repeat domain (HR1), two transmembrane domains, and a second heptad repeat domain (HR...
Article
Full-text available
Mitochondria are dynamic organelles that continually move, fuse and divide. The dynamic balance of fusion and fission of mitochondria determines their morphology and allows their immediate adaptation to energetic needs, keeps mitochondria in good health by restoring or removing damaged organelles or precipitates cells in apoptosis in cases of sever...
Article
Full-text available
Mitochondria are highly dynamic organelles that continuously move, fuse and divide. Mitochondrial dynamics modulate overall mitochondrial morphology and are essential for the proper function, maintenance and transmission of mitochondria and mitochondrial DNA (mtDNA). We have investigated mitochondrial fusion in yeast cells with severe defects in ox...
Article
Mitochondrial dysfunction and perturbed degradation of proteins have been implicated in Parkinson's disease (PD) pathogenesis. Mutations in the Parkin and PINK1 genes are a cause of familial PD. PINK1 is a putative kinase associated with mitochondria, and loss of PINK1 expression leads to mitochondrial dysfunction, which increases with time. Parkin...
Article
Full-text available
Mitochondria are dynamic organelles that continuously move, fuse and divide. Their overall morphology, ranging from a filamentous network to a collection of isolated dots, is determined by fusion-fission equilibrium, which depends on the cellular and physiological context. The machineries of fusion and fission, that are conserved throughout evoluti...
Article
Opa1 modulates mitochondrial fusion, cristae structure and apoptosis. The relationships between these functions and autosomal dominant optic atrophy, caused by mutations in Opa1, are poorly defined. We show that Bnip3 interacts with Opa1, leading to mitochondrial fragmentation and apoptosis. Fission is due to inhibition of Opa1-mediated fusion and...
Article
Mitochondria are the site where oxidative phosphorylations (OXPHOSs) take place. Fusion and fission reactions allow them to change their overall morphology, which ranges from networks of elongated and branched filaments to collections of small individual organelles. It is assumed that mitochondrial bioenergetics and dynamics are linked and that mit...
Article
Human OPA1 (optic atrophy type 1) is a dynamin-related protein of the mitochondrial IMS (intermembrane space) involved in membrane fusion and remodelling. Similarly to its yeast orthologue Mgm1p that exists in two isoforms generated by the serine protease Pcp1p/Rbd1p, OPA1 exists in various isoforms generated by alternative splicing and processing....
Article
Mitochondria are dynamic organelles with continuous fusion and fission, the equilibrium of which results in mitochondrial morphology. Evidence points to there being an intricate relationship between mitochondrial dynamics and oxidative phosphorylation. We investigated the bioenergetics modulation of mitochondrial morphology in five control cultured...
Article
Full-text available
There is no evidence to date on whether transcriptional regulators are able to shift the balance between mitochondrial fusion and fission events through selective control of gene expression. Here, we demonstrate that reduced mitochondrial size observed in knock-out mice for the transcriptional regulator PGC-1beta is associated with a selective redu...
Article
Full-text available
Mitochondria form a dynamic network in which continuous movement, fusion, and division ensure the distribution and exchange of proteins and deoxyribonucleic acid (DNA). The recent past has seen the identification and characterization of the first proteins governing the organization, function, and dynamics of mitochondria and mitochondrial DNA, and...
Article
Mitochondria are almost ubiquitous organelles in Eukaryota. They are highly dynamic and often complex structures in the cell. The mammalian mitochondrial proteome is predicted to comprise as many as 2000-2500 different proteins. Determination of the subcellular localization of any newly identified protein is one of the first steps toward unraveling...
Article
Enlarged or giant mitochondria have often been documented in aged tissues although their role and underlying mechanism remain unclear. We report here how highly elongated giant mitochondria are formed in and related to the senescent arrest. The mitochondrial morphology was progressively changed to a highly elongated form during deferoxamine (DFO)-i...
Article
Eukaryotic cells contain numerous copies of the mitochondrial genome (from 50 to 100 copies in the budding yeast to some thousands in humans) that localize to numerous intramitochondrial nucleoprotein complexes called nucleoids. The transmission of mitochondrial DNA differs significantly from that of nuclear genomes and depends on the number, molec...
Article
The International FEBS-IUBMB Workshop: 'Mitochondrial Dynamics in Cell Life and Death', 27–30 August 2005, was dedicated to the memory of Stanley J Korsmeyer (1950–2005). It was held at the Venetian Institute of Molecular Medicine in Padova, a charming city near Venice that hosts a respected university with a long-standing tradition for scientific...
Conference Paper
The International FEBS-IUBMB Workshop: 'Mitochondrial Dynamics in Cell Life and Death', 27–30 August 2005, was dedicated to the memory of Stanley J Korsmeyer (1950–2005). It was held at the Venetian Institute of Molecular Medicine in Padova, a charming city near Venice that hosts a respected university with a long-standing tradition for scientific...
Article
Full-text available
Mitochondria are enveloped by two closely apposed boundary membranes with different properties and functions. It is known that they undergo fusion and fission, but it has remained unclear whether outer and inner membranes fuse simultaneously, coordinately or separately. We set up assays for the study of inner and outer membrane fusion in living hum...
Article
Full-text available
Heteroplasmic mutations of mitochondrial DNA (mtDNA) are an important source of human diseases. The mechanisms governing transmission, segregation and complementation of heteroplasmic mtDNA-mutations are unknown but depend on the nature and dynamics of the mitochondrial compartment as well as on the intramitochondrial organization and mobility of m...
Article
Mitochondria are essential organelles that are involved in numerous metabolic pathways and produce the major part of intracellular ATP by oxidative phosphorylation. Their ultrastructure was solved in the 1950s by electron microscopic analysis of ultrathin sections. Based on these pioneering studies and on the endosymbiotic origin of mitochondria, c...
Article
Mitochondria are essential organelles that are involved in numerous metabolic pathways and produce the major part of intracellular ATP by oxidative phosphorylation. Their ultrastructure was solved in the 1950s by electron microscopic analysis of ultrathin sections. Based on these pioneering studies and on the endosymbiotic origin of mitochondria, c...
Article
Full-text available
Trans-membrane proteins of the p24 family are abundant, oligomeric proteins predominantly found in cis-Golgi membranes. They are not easily studied in vivo and their functions are controversial. We found that p25 can be targeted to the plasma membrane after inactivation of its canonical KKXX motif (KK to SS, p25SS), and that p25SS causes the co-tra...
Article
Mitochondrial fusion remains a largely unknown process despite its observation by live microscopy and the identification of few implicated proteins. Using green and red fluorescent proteins targeted to the mitochondrial matrix, we show that mitochondrial fusion in human cells is efficient and achieves complete mixing of matrix contents within 12 h....
Article
Two human Fzo-homologs, mitofusins Mfn1 and Mfn2, are shown by RT-PCR and western blot to be ubiquitous mitochondrial proteins. Protease digestion experiments reveal that Mfn2 is an outer membrane protein with N-terminal and C-terminal domains exposed towards the cytosol. The transmembrane and C-terminal domains of Mfn2 (Mfn2-TMCT) are targeted to...
Article
The extent of intermitochondrial molecular exchanges is highly relevant to the therapeutic prospects of human diseases associated with heteroplasmic alterations of the mitochondrial DNA (mtDNA). However, the efficiency of mitochondrial fusion and the diffusion characteristics of mitochondrial components remain essentially unknown in humans. We addr...
Article
Full-text available
Recent studies show that small trans-membrane proteins of approximately 22-24 kDa (the p24 family), which are grouped into 4 sub-families by sequence homology (p23, p24, p25 and p26), are involved in the early secretory pathway. In this study, we have investigated the mutual requirements of ectopically expressed members of the p24 family for target...
Article
Full-text available
In previous studies we have shown that p23, a member of the p24-family of small transmembrane proteins, is highly abundant in membranes of the cis-Golgi network (CGN), and is involved in sorting/trafficking in the early secretory pathway. In the present study, we have further investigated the role of p23 after ectopic expression. We found that ecto...
Article
Full-text available
Dbp6p is an essential putative ATP-dependent RNA helicase that is required for 60S-ribosomal-subunit assembly in the yeastSaccharomyces cerevisiae (D. Kressler, J. de la Cruz, M. Rojo, and P. Linder, Mol. Cell. Biol. 18:1855–1865, 1998). To identify factors that are functionally interacting with Dbp6p, we have performed a synthetic lethal screen wi...
Article
Full-text available
Several mutants (spb1-spb7) have been previously identified as cold-sensitive extragenic suppressors of loss-of-function mutations in the poly(A)+-binding protein 1 of Saccharomyces cerevisiae. Cloning, sequence and disruption analyses revealed that SPB1 (YCL054W) encodes an essential putative S-adenosyl-methionine-dependent methyltransferase. Poly...
Article
Full-text available
The p24 family of small transmembrane proteins was discovered recently in yeast and mammalian cells, and some of its members have been implicated in biosynthetic protein transport. The p24 proteins are proposed to act on transport vesicles as receptors for coat and/or cargo, but their precise function(s) remain controversial. Here, we describe this...
Article
Full-text available
Spb4p is a putative ATP-dependent RNA helicase that is required for synthesis of 60S ribosomal subunits. Polysome analyses of strains genetically depleted of Spb4p or carrying the cold-sensitive spb4-1 mutation revealed an underaccumulation of 60S ribosomal subunits. Analysis of pre-rRNA processing by pulse-chase labeling, northern hybridization, a...
Article
Full-text available
A previously uncharacterized Saccharomyces cerevisiae open reading frame, YNR038W, was analyzed in the context of the European Functional Analysis Network. YNR038W encodes a putative ATP-dependent RNA helicase of the DEAD-box protein family and was therefore named DBP6 (DEAD-box protein 6). Dbp6p is essential for cell viability. In vivo depletion o...
Article
Full-text available
Here, we report the localization and characterization of BHKp23, a member of the p24 family of transmembrane proteins, in mammalian cells. We find that p23 is a major component of tubulovesicular membranes at the cis side of the Golgi complex (estimated density: 12,500 copies/micron2 membrane surface area, or approximately 30% of the total protein)...
Article
Full-text available
A previously uncharacterized Saccharomyces cerevisiae gene, FAL1, was found by sequence comparison as a homolog of the eukaryotic translation initiation factor 4A (eIF4A). Fal1p has 55% identity and 73% similarity on the amino acid level to yeast eIF4A, the prototype of ATP-dependent RNA helicases of the DEAD-box protein family. Although clearly gr...
Article
Intracellular membranes are highly dynamic, yet they retain their identity and functional characteristics. Integral membrane proteins, which must confer this specific membrane identity, remain poorly characterized at the biochemical level, largely because detergent-mediated solubilization is required for purification and analysis, and several prope...
Article
Full-text available
The interaction of several classes of detergents with mitochondrial ATP/ADP carrier (AAC) was studied. The detergents that were best suited for solubilization of active AAC differed in several physico-chemical properties, but contained relatively rigid or planar hydrophobic (sub)moieties. Based on specific binding of AAC to Blue Sepharose, a novel...
Article
Full-text available
The biochemical and biophysical characterization of the mitochondrial creatine kinase (Mi-CK) from chicken cardiac muscle is reviewed with emphasis on the structure of the octameric oligomer by electron microscopy and on its membrane binding properties. Information about shape, molecular symmetry and dimensions of the Mi-CK octamer, as obtained by...
Article
Full-text available
Purified mitochondrial creatine kinase (Mi-CK) (EC 2.7.3.2) from chicken heart was shown to interact simultaneously with purified inner and outer mitochondrial membranes, thereby creating an intermembrane chondrial membranes, thereby creating an intermembrane were purified from rat liver and thus were fully devoid of Mi-CK. Intermembrane contact fo...
Article
Full-text available
The interaction of mitochondrial creatine kinase (Mi-CK; EC 2.7.3.2) with phospholipid monolayers and spread mitochondrial membranes at the air/water interface has been investigated. It appeared that Mi-CK penetrated into these monolayers as evidenced by an increase in surface pressure upon incorporation of Mi-CK. The increase in surface pressure w...
Article
Full-text available
Three functions have been suggested to be localized in contact sites between the inner and the outer membrane of mitochondria from mammalian cells: (i) transfer of energy from matrix to cytosol through the action of peripheral kinases; (ii) import of mitochondrial precursor proteins; and (iii) transfer of lipids between outer and inner membrane. In...

Network

Cited By