Isolation, Mapping, and Genomic Structure of an X-Linked Gene for a Subunit of Human Mitochondrial Complex I

Zhuchenko, Olga; Wehnert, Manfred; Bailey, Jennifer M.; Sun, Zhong Sheng; Lee, Cheng‐Chi

doi:10.1006/geno.1996.0561

Cited by 47 publications

(25 citation statements)

References 2 publications

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“…However, it is known that some soluble proteins with dual subcellular localization can be targeted to the mitochondrial matrix without the aid of a canonical MTS, such as 2-methylacyl-CoA racemase (Amery et al, 2000). Furthermore, mitochondrial proteins that are associated with the matrix side of the mitochondrial IM, such as the accessory subunit of complex I, MWFE, are imported without an MTS (Zhuchenko et al, 1996). Although primary sequence analysis of SOD1 reveals no obvious MTS, SOD1 may contain a cryptic importation signal, and it may follow mitochondrial importation pathways similar to those of these proteins.…”

Section: Discussionmentioning

confidence: 99%

Mutant Superoxide Dismutase 1 Forms Aggregates in the Brain Mitochondrial Matrix of Amyotrophic Lateral Sclerosis Mice

Vijayvergiya¹,

Beal²,

Buck³

et al. 2005

J. Neurosci.

217

165

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An increasing body of evidence suggests that mitochondrial dysfunction plays an important role in the pathogenesis of familial amyotrophic lateral sclerosis associated with "gain of function" mutations in Cu/Zn superoxide dismutase 1 (SOD1). SOD1 is mostly a cytosolic protein, but a portion of SOD1 is localized in mitochondria of patients with familial amyotrophic lateral sclerosis and transgenic mouse models of the disease. Despite the finding that mutant SOD1 localizes in mitochondria, the pathogenic significance of the mitochondrial mutant SOD1 remains to be elucidated. Here, we demonstrate that both wild-type and mutant human SOD1 accumulate in brain mitochondria of transgenic mice and that SOD1 displays a very complex intramitochondrial compartmentalization. For the first time, we show that, in addition to being in the mitochondrial outer membrane and intermembrane space, SOD1 is also localized in the mitochondrial matrix. Importantly, we show that aberrant SOD1 macromolecular aggregates are formed in the matrix of brain mitochondria. This suggests that mutant SOD1 in the brain mitochondrial matrix is misfolded and prone to aggregation, which may contribute to selective neuronal degeneration.

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Section: Discussionmentioning

confidence: 99%

Mutant Superoxide Dismutase 1 Forms Aggregates in the Brain Mitochondrial Matrix of Amyotrophic Lateral Sclerosis Mice

Vijayvergiya¹,

Beal²,

Buck³

et al. 2005

J. Neurosci.

217

165

View full text Add to dashboard Cite

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“…Finally, it is worth noting that subunits ESSS and MWFE are the only subunits of human complex I to be found on the X chromosome (15,38). The promoter region of the NDUFA1 gene encoding subunit MWFE contains a cAMP response element, suggesting that expression of this subunit is linked to cAMP signaling pathways that regulate cellular energy metabolism (38).…”

Section: Identities Of Phosphorylated Proteins In Bovinementioning

confidence: 99%

“…The promoter region of the NDUFA1 gene encoding subunit MWFE contains a cAMP response element, suggesting that expression of this subunit is linked to cAMP signaling pathways that regulate cellular energy metabolism (38). It is not known whether the gene for ESSS is regulated in a similar way.…”

Section: Identities Of Phosphorylated Proteins In Bovinementioning

confidence: 99%

The Phosphorylation of Subunits of Complex I from Bovine Heart Mitochondria

Chen

Fearnley

Peak‐Chew

et al. 2004

Journal of Biological Chemistry

149

102

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In bovine heart mitochondria and in submitochondrial particles, membrane-associated proteins with apparent molecular masses of 18 and 10 kDa become strongly radiolabeled by [ 32 P]ATP in a cAMP-dependent manner. The 18-kDa phosphorylated protein is subunit ESSS from complex I and not as previously reported the 18 k subunit (with the N-terminal sequence AQDQ). The phosphorylated residue in subunit ESSS is serine 20. In the 10 kDa band, the complex I subunit MWFE was phosphorylated on serine 55. In the presence of protein kinase A and cAMP, the same subunits of purified complex I were phosphorylated by [ 32 P]ATP at the same sites. Subunits ESSS and MWFE both contribute to the membrane arm of complex I. Each has a single hydrophobic region probably folded into a membrane spanning ␣-helix. It is likely that the phosphorylation site of subunit ESSS lies in the mitochondrial matrix and that the site in subunit MWFE is in the intermembrane space. Subunit ESSS has no known role, but subunit MWFE is required for assembly into complex I of seven hydrophobic subunits encoded in the mitochondrial genome. The possible effects of phosphorylation of these subunits on the activity and/or the assembly of complex I remain to be explored.

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“…Sequence analysis suggests that this transcript encodes a protein of 261 aa related to the short-chain alcohol dehydrogenase family (Prosite database, accession no. PS00061) (40). Another selected cDNA, ADS40, mapped adjacent to an EST, NIB723, within the YAC contig (Fig.…”

Section: Identification Of Expressed Sequencesmentioning

confidence: 99%

Chromosomal basis of X chromosome inactivation: Identification of a multigene domain in Xp11.21-p11.22 that escapes X inactivation

Miller

Willard

1998

Proc. Natl. Acad. Sci. U.S.A.

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A number of genes have been identified that escape mammalian X chromosome inactivation and are expressed from both active and inactive X chromosomes. The basis for escape from inactivation is unknown and, a priori, could be a result of local factors that act in a gene-specific manner or of chromosomal control elements that act regionally. Models invoking the latter predict that such genes should be clustered in specific domains on the X chromosome, rather than distributed at random along the length of the X. To distinguish between these possibilities, we have constructed a transcription map composed of at least 23 distinct expressed sequences in an Ϸ5.5-megabase region on the human X chromosome spanning Xp11.21-p11.22. The inactivation status of these transcribed sequences has been determined in a somatic cell hybrid system and correlated with the position of the genes on the physical map. Although the majority of transcribed sequences in this region are subject to X inactivation, eight expressed sequences (representing at least six different genes) escape inactivation, and all are localized to within a region of less than 370 kb. Genes located both distal and proximal to this cluster are subject to inactivation, thereby defining a unique multigene domain on the proximal short arm that is transcriptionally active on the inactive X chromosome.

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Isolation, Mapping, and Genomic Structure of an X-Linked Gene for a Subunit of Human Mitochondrial Complex I

Cited by 47 publications

References 2 publications

Mutant Superoxide Dismutase 1 Forms Aggregates in the Brain Mitochondrial Matrix of Amyotrophic Lateral Sclerosis Mice

Mutant Superoxide Dismutase 1 Forms Aggregates in the Brain Mitochondrial Matrix of Amyotrophic Lateral Sclerosis Mice

The Phosphorylation of Subunits of Complex I from Bovine Heart Mitochondria

Chromosomal basis of X chromosome inactivation: Identification of a multigene domain in Xp11.21-p11.22 that escapes X inactivation

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