Sequence and organization of the human mitochondrial genome

Anderson, Stephen; Bankier, Alan T.; Barrell, Bart; Bruijn, M.H.L. de; Coulson, Alan; Drouin, Jacques; Eperon, Ian C.; Nierlich, Donald P.; Roe, Bruce A.; Sanger, F.; Schreier, Peter; Smith, Andrew J.H.; Staden, Rodger; Young, Ian G.

doi:10.1038/290457a0

Cited by 8,560 publications

(5,379 citation statements)

References 57 publications

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“…products in rat liver, corresponding approximately to the number of reading frames identified on human and bovine mitochondrial DNA [ 1]. This agrees with the findings in several human celt lines [5] but not with recent reports [2,4] that 25 translation products can be separated in Hela cell mitochondria using twodimensional electrophoresis, and as many as 18 products can be separated in a single dimension [2,4].…”

Section: ¸¸¸6¸¸supporting

confidence: 88%

“…Although it is now clear that up to 13 peptides may be encoded in mammalian mitochondrial DNA [ 1 ], there is little agreement concerning the numbers of stable translation products detectable in these mitochondria [2][3][4][5]. Part of this uncertainty is due to the low rates of labeling of mammalian mitochondrial translations products resulting from the relatively slow growth rates of mammalian cells.…”

Section: Introductionmentioning

confidence: 99%

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Translation of mitochondrial proteins in digitonin‐treated rat hepatocytes

1981

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Section: ¸¸¸6¸¸supporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Translation of mitochondrial proteins in digitonin‐treated rat hepatocytes

1981

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“…The human mitochondrial genome encodes only 22 tRNAs. This necessitates the use of wobble base pairings to permit the entire set of codon:anticodon interactions 30 . Since the use of a wobble represents an imperfect codon;anticodon it was possible that such mismatches could affect the dwell time of some aminoacylated mt-tRNA within the mitoribosome.…”

Section: Resultsmentioning

confidence: 99%

Using mitoribosomal profiling to investigate human mitochondrial translation

et al. 2017

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Background: Gene expression in human mitochondria has various idiosyncratic features. One of these was recently revealed as the unprecedented recruitment of a mitochondrially-encoded tRNA as a structural component of the large mitoribosomal subunit. In porcine particles this is mt-tRNA Phe whilst in humans it is mt-tRNA Val. We have previously shown that when a mutation in mt-tRNA Val causes very low steady state levels, there is preferential recruitment of mt-tRNA Phe. We have investigated whether this altered mitoribosome affects intra-organellar protein synthesis. Methods: By using mitoribosomal profiling we have revealed aspects of mitoribosome behaviour with its template mt-mRNA under both normal conditions as well as those where the mitoribosome has incorporated mt-tRNA Phe. Results: Analysis of the mitoribosome residency on transcripts under control conditions reveals that although mitochondria employ only 22 mt-tRNAs for protein synthesis, the use of non-canonical wobble base pairs at codon position 3 does not cause any measurable difference in mitoribosome occupancy irrespective of the codon. Comparison of the profile of aberrant mt-tRNA Phe containing mitoribosomes with those of controls that integrate mt-tRNA Val revealed that the impaired translation seen in the latter was not due to stalling on triplets encoding either of these amino acids. The alterations in mitoribosome interactions with start codons was not directly attributable to the either the use of non-cognate initiation codons or the presence or absence of 5’ leader sequences, except in the two bicistronic RNA units, RNA7 and RNA14 where the initiation sites are internal. Conclusions: These data report the power of mitoribosomal profiling in helping to understand the subtleties of mammalian mitochondrial protein synthesis. Analysis of profiles from the mutant mt-tRNA Val cell line suggest that despite mt-tRNA Phe being preferred in the porcine mitoribosome, its integration into the human counterpart results in a suboptimal structure that modifies its interaction with mt-mRNAs.

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“…Cells were harvested and the DNA was extracted by the phenol/ chloroform method, as described elsewhere [20]. mtDNA amplification was performed by PCR, using the following set of primers: np 3148-3167 (forward) 5'-CCTACTTCACAAAGCGCCTT-3' and np 3531-3550 (reverse) 5'-CGATGGTGAGAGCTAAGGTC-Y (nucleotide numbering according to [20]).…”

Section: Mtdna Analysismentioning

confidence: 99%

mtDNA‐depleted U937 cells are sensitive to TNF and Fas‐mediated cytototxicity

et al. 1995

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It has been proposed that TNF cytotoxicity is mediated by reactive oxygen intermediates generated by uncoupling of mitochondrial respiration. We have compared sensitive U937 cells and derived cell lines depleted of mtDNA for their ability to undergo TNF-and Fas-induced apoptosis. Cells lacking around 98% of mtDNA were still sensitive to TNF-induced apoptosis. U937 cells devoid of mtDNA (U937-p °) were resistant to TNF, but this was due to the loss of its 55 kDa receptor. U937-p ° cells were also resistant to docosahexaenoic acid, which causes U937 cell death by lipid peroxidation. These cells were sensitive to anti-Fas toxicity. The results indicate that TNF and Fasinduced toxicity occurs by a mechanism mostly independent of mitochondrial free radical generation.The mechanism by which Fas ligation triggers apoptosis, as well as a general biochemical mechanism for the apoptosis process itself, are unknown [5]. Some reports have suggested, however, the lack of implication of oxidative damage in cytotoxicity induced with anti-Fas, using antioxidants [14,15] or anaerobic conditions [16].In the present work, we have studied the effect of TNF and anti-Fas on U937 cells and in derived cell lines depleted of mtDNA by prolonged exposure to low doses of ethidium bromide. Results indicate that impairment of mitochondrial function and lipid peroxidation do not play a key role in the apoptosis induced by both molecules in human myeloid cells.

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Sequence and organization of the human mitochondrial genome

Cited by 8,560 publications

References 57 publications

Translation of mitochondrial proteins in digitonin‐treated rat hepatocytes

Translation of mitochondrial proteins in digitonin‐treated rat hepatocytes

Using mitoribosomal profiling to investigate human mitochondrial translation

mtDNA‐depleted U937 cells are sensitive to TNF and Fas‐mediated cytototxicity

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