Structural and Regulatory Mutations Affecting Mitochondrial Gene Products

1977 ◽  
pp. 345-370 ◽  
Author(s):  
H. R. Mahler ◽  
D. Hanson ◽  
D. Miller ◽  
T. Bilinski ◽  
D. M. Ellis ◽  
...  
Keyword(s):  
Mitochondrial Gene ◽  
Gene Products ◽  
Regulatory Mutations

scholarly journals Profiling subcellular localization of nuclear-encoded mitochondrial gene products in zebrafish

2021 ◽  
Author(s):  
Barbara Uszczynska-Ratajczak ◽  
Sreedevi Sugunan ◽  
Monika Kwiatkowska ◽  
Maciej Migdal ◽  
Silvia Carbonell-Sala ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Protein Import ◽  
Mitochondrial Gene ◽  
Mitochondrial Protein ◽  
Mitochondrial Fraction ◽  
Mitochondrial Proteins ◽  
Gene Products ◽  
Messenger Rnas ◽  
Mitochondrial Transcripts ◽  
Transcriptomic Changes

Most mitochondrial proteins are encoded by nuclear genes, synthetized in the cytosol and targeted into the organelle. The import of some, but not all, nuclear-encoded mitochondrial proteins begins with translation of messenger RNAs (mRNAs) on the surface of mitochondria. To characterize the spatial organization of mitochondrial gene products in zebrafish (Danio rerio), we sequenced RNA from different cellular fractions. Our results confirmed the presence of nuclear-encoded mRNAs in the mitochondrial fraction, which in unperturbed conditions, are mainly transcripts encoding large proteins with specific properties, like transmembrane domains. To further explore the principles of mitochondrial protein compartmentalization in zebrafish, we quantified the transcriptomic changes for each subcellular fraction triggered by the chchd4a-/- mutation, causing the disorders in the mitochondrial protein import. Our results indicate that the proteostatic stress further restricts the population of transcripts on the mitochondrial surface, allowing only the largest and the most evolutionary conserved proteins to be synthetized there. We also show that many nuclear-encoded mitochondrial transcripts translated by the cytosolic ribosomes stay resistant to the global translation shutdown. Thus, vertebrates, in contrast to yeast, are not likely to employ localized translation to facilitate synthesis of mitochondrial proteins under proteostatic stress conditions.

Identification of Paramecium mitochondrial proteins using antibodies raised against fused mitochondrial gene products

Gene ◽  
1986 ◽  
Vol 49 (1) ◽  
pp. 129-138 ◽  
Author(s):  
Ravi Mahalingam ◽  
Jeffrey J. Seilhamer ◽  
Arthur E. Pritchard ◽  
Donald J. Cummings
Keyword(s):  
Mitochondrial Gene ◽  
Mitochondrial Proteins ◽  
Gene Products

scholarly journals Identification of the subunits of bovine NADH dehydrogenase which are encoded by the mitochondrial genome

1990 ◽  
Vol 265 (3) ◽  
pp. 903-906 ◽  
Author(s):  
G M Gibb ◽  
C I Ragan
Keyword(s):  
Mitochondrial Genome ◽  
Hela Cell ◽  
Cell Line ◽  
Gel Electrophoresis ◽  
Nadh Dehydrogenase ◽  
Mitochondrial Gene ◽  
Gene Products ◽  
Hela Cell Line ◽  
Kidney Cell Line ◽  
Bovine Kidney

Products of the mitochondrial genome were identified in the bovine kidney cell line NBL-1 by labelling with [35S]methionine in the presence of cycloheximide. Seven proteins were precipitated by an antiserum to bovine heart NADH dehydrogenase, corresponding to the seven mitochondrial gene products identified in the human HeLa cell line. Comparison of these mitochondrial gene products with purified bovine NADH dehydrogenase by SDS/gel electrophoresis revealed that the ND-5 product is probably a previously unidentified protein of apparent Mr 51,000, and the ND-4 product is the protein of apparent Mr 39,000.

scholarly journals Modular assembly of yeast cytochrome oxidase

2013 ◽  
Vol 24 (4) ◽  
pp. 440-452 ◽  
Author(s):  
Gavin P. McStay ◽  
Chen Hsien Su ◽  
Alexander Tzagoloff
Keyword(s):  
Molecular Weight ◽  
Cytochrome Oxidase ◽  
High Molecular Weight ◽  
Mitochondrial Gene ◽  
Gene Products ◽  
Modular Assembly ◽  
Isolated Mitochondria ◽  
Assembly Factors ◽  
The Individual ◽  
Individual Core

Previous studies of yeast cytochrome oxidase (COX) biogenesis identified Cox1p, one of the three mitochondrially encoded core subunits, in two high–molecular weight complexes combined with regulatory/assembly factors essential for expression of this subunit. In the present study we use pulse-chase labeling experiments in conjunction with isolated mitochondria to identify new Cox1p intermediates and place them in an ordered pathway. Our results indicate that before its assimilation into COX, Cox1p transitions through five intermediates that are differentiated by their compositions of accessory factors and of two of the eight imported subunits. We propose a model of COX biogenesis in which Cox1p and the two other mitochondrial gene products, Cox2p and Cox3p, constitute independent assembly modules, each with its own complement of subunits. Unlike their bacterial counterparts, which are composed only of the individual core subunits, the final sequence in which the mitochondrial modules associate to form the holoenzyme may have been conserved during evolution.

scholarly journals Assembly of the peripheral stalk of ATP synthase in human mitochondria

2020 ◽  
Vol 117 (47) ◽  
pp. 29602-29608
Author(s):  
Jiuya He ◽  
Joe Carroll ◽  
Shujing Ding ◽  
Ian M. Fearnley ◽  
Martin G. Montgomery ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Mitochondrial Gene ◽  
Nuclear Genes ◽  
Gene Products ◽  
Alternative Pathways ◽  
Peripheral Stalk ◽  
Membrane Bound ◽  
Membrane Components ◽  
Subunit B ◽  
Cytoplasmic Ribosomes

The adenosine triphosphate (ATP) synthase in human mitochondria is a membrane bound assembly of 29 proteins of 18 kinds organized into F1-catalytic, peripheral stalk (PS), and c8-rotor ring modules. All but two membrane components are encoded in nuclear genes, synthesized on cytoplasmic ribosomes, imported into the mitochondrial matrix, and assembled into the complex with the mitochondrial gene products ATP6 and ATP8. Intermediate vestigial ATPase complexes formed by disruption of nuclear genes for individual subunits provide a description of how the various domains are introduced into the enzyme. From this approach, it is evident that three alternative pathways operate to introduce the PS module (including associated membrane subunits e, f, and g). In one pathway, the PS is built up by addition to the core subunit b of membrane subunits e and g together, followed by membrane subunit f. Then this b-e-g-f complex is bound to the preformed F1-c8module by subunits OSCP and F6. The final component of the PS, subunit d, is added subsequently to form a key intermediate that accepts the two mitochondrially encoded subunits. In another route to this key intermediate, first e and g together and then f are added to a preformed F1-c8-OSCP-F6-b-d complex. A third route involves the addition of the c8-ring module to the complete F1-PS complex. The key intermediate then accepts the two mitochondrially encoded subunits, stabilized by the addition of subunit j, leading to an ATP synthase complex that is coupled to the proton motive force and capable of making ATP.

scholarly journals Mitochondrial gene expression in Saccharomyces cerevisiae. Proteolysis of nascent chains in isolated yeast mitochondria optimized for protein synthesis

1991 ◽  
Vol 274 (1) ◽  
pp. 199-205 ◽  
Author(s):  
C L Black-Schaefer ◽  
J D McCourt ◽  
R O Poyton ◽  
E E McKee
Keyword(s):  
Protein Synthesis ◽  
Mitochondrial Gene ◽  
Mitochondrial Protein ◽  
Gene Products ◽  
Yeast Mitochondria ◽  
Mitochondrial Translation ◽  
True Rate ◽  
Isolated Mitochondria ◽  
Enzyme Complexes

We demonstrate here that mitochondrial translation products synthesized by isolated yeast mitochondria are subject to rapid proteolysis. The loss of label from mitochondrial peptides synthesized in vitro comes from two distinct pools of peptides: one that is rapidly degraded (t1/2 of minutes) and one that is much more resistant to proteolysis (t1/2 of hours). As the length of the incubation period increases, the percentage of labelled peptides in the rapidly-turning-over pool decreases and cannot be detected after 60 min of incubation. This proteolysis is inhibited by chloramphenicol and is dependent on the presence of ATP. The loss of label during the chase occurs from fully completed translation products. The proteolysis observed here markedly affects measurements of rates of mitochondrial protein synthesis in isolated yeast mitochondria. In earlier work, in which proteolysis was not considered, mitochondrial translation was thought to stop after 20-30 min of incubation. In the present study, by taking proteolysis into account, we demonstrate that the rate of translation in isolated mitochondria is actually constant for nearly 60 min and then decreases to near zero by 80 min of incorporation. These findings have allowed us to devise a procedure for measuring the ‘true’ rate of translation in isolated mitochondria. In addition, they suggest that mitochondrial translation products which normally assemble with nuclear-encoded gene products into multimeric enzyme complexes are unstable without their nuclear-encoded counterparts.

scholarly journals TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase and interact with assembly factors for complex I

2021 ◽  
Vol 118 (13) ◽  
pp. e2100558118
Author(s):  
Joe Carroll ◽  
Jiuya He ◽  
Shujing Ding ◽  
Ian M. Fearnley ◽  
John E. Walker
Keyword(s):  
Atp Synthase ◽  
Complex I ◽  
Transmembrane Protein ◽  
Mitochondrial Gene ◽  
Nuclear Gene ◽  
Gene Products ◽  
Mitochondrial Atp Synthase ◽  
Complex I Assembly ◽  
The Impact ◽  
Enzyme Complexes

Human mitochondrial ATP synthase is a molecular machine with a rotary action bound in the inner organellar membranes. Turning of the rotor, driven by a proton motive force, provides energy to make ATP from ADP and phosphate. Among the 29 component proteins of 18 kinds, ATP6 and ATP8 are mitochondrial gene products, and the rest are nuclear gene products that are imported into the organelle. The ATP synthase is assembled from them via intermediate modules representing the main structural elements of the enzyme. One such module is the c8-ring, which provides the membrane sector of the enzyme’s rotor, and its assembly is influenced by another transmembrane (TMEM) protein, TMEM70. We have shown that subunit c interacts with TMEM70 and another hitherto unidentified mitochondrial transmembrane protein, TMEM242. Deletion of TMEM242, similar to deletion of TMEM70, affects but does not completely eliminate the assembly of ATP synthase, and to a lesser degree the assembly of respiratory enzyme complexes I, III, and IV. Deletion of TMEM70 and TMEM242 together prevents assembly of ATP synthase and the impact on complex I is enhanced. Removal of TMEM242, but not of TMEM70, also affects the introduction of subunits ATP6, ATP8, j, and k into the enzyme. TMEM70 and TMEM242 interact with the mitochondrial complex I assembly (the MCIA) complex that supports assembly of the membrane arm of complex I. The interactions of TMEM70 and TMEM242 with MCIA could be part of either the assembly of ATP synthase and complex I or the regulation of their levels.

scholarly journals Aep3p-dependent translation of yeast mitochondrial ATP8

2017 ◽  
Vol 28 (11) ◽  
pp. 1426-1434 ◽  
Author(s):  
Mario H. Barros ◽  
Alexander Tzagoloff
Keyword(s):  
Mitochondrial Gene ◽  
Nuclear Gene ◽  
Untranslated Regions ◽  
Temperature Sensitive ◽  
Permissive Temperature ◽  
Gene Products ◽  
Expression Plasmid ◽  
Mitochondrial Ribosomes ◽  
Recessive Mutations ◽  
Initiation Of Translation

Translation of mitochondrial gene products in Saccharomyces cerevisiae depends on mRNA-specific activators that bind to the 5’ untranslated regions and promote translation on mitochondrial ribosomes. Here we find that Aep3p, previously shown to stabilize the bicistronic ATP8-ATP6 mRNA and facilitate initiation of translation from unformylated methionine, also activates specifically translation of ATP8. This is supported by several lines of evidence. Temperature-sensitive aep3 mutants are selectively blocked in incorporating [35S]methionine into Atp8p at nonpermissive but not at the permissive temperature. This phenotype is not a consequence of defective transcription or processing of the pre-mRNA. Neither is it explained by turnover of Aep3p, as evidenced by the failure of aep3 mutants to express a recoded ARG8m when this normally nuclear gene is substituted for ATP8 in mitochondrial DNA. Finally, translational of ATP8 mRNA in aep3 mutants is partially rescued by recoded allotopic ATP8 (nATP8) in a high-expression plasmid or in a CEN plasmid in the presence of recessive mutations in genes involved in stability and polyadenylation of RNA.

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