User:Mmaetani

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transporter protein that enables ATP and ADP to transverse the inner mitochondrial membrane. ATP is transported from the mitochondrial matrix, where it is produced by oxidative phosphorylation, to the cytoplasm, whereas ADP is transported from the cytoplasm to the mitochondrial matrix.[1] More than 10% of the protein in the inner mitochondrial membrane consists of ATP/ADP translocase.[2]

Structure

isoforms, and has a maximal diameter of 20 A and a depth of 30 A.[4] Indeed, arginine 96, 204, 252, 253, and 294, as well as lysine 38, have been shown to be essential for transporter activity.[5]

Translocase Mechanism

Under normal conditions, ATP and ADP cannot cross the inner mitochondrial membrane due to their high negative charges, but ATP/ADP translocase, an

nucleotides
recognized by the translocase.

The net process is denoted by:

ATP3-cytoplasm + ATP4-matrix → ATP3-matrix + ATP4-cytoplasm

ATP-ADP exchange is energetically expensive: about 25% of the energy yielded from electron transfer by aerobic respiration, or one hydrogen ion, is consumed to regenerate the membrane potential that is tapped by ATP/ADP translocase.[1]

History

In 1955, Siekevitz and Potter

cDNA of ATP/ADP translocase was sequenced for bovine in 1982[12] and a yeast species Saccharomyces cerevisiae in 1986[13] before finally Battini et al. sequenced a cDNA clone of the human transporter in 1989. The homology in the coding sequences between human and yeast ATP/ADP translocase was 47% while bovine and human sequences extended remarkable to 266 out of 297 residues, or 89.6%. In both cases, the most conserved residues lie in the ATP/ADP substrate binding pocket.[3]

Regulation & Inhibition

Rare but severe diseases such as

introns, or non-coding regions of DNA, which increases the likelihood of deleterious mutations. Thus, any modification of ATP/ADP translocase mtDNA can lead to a dysfunctional transporter,[16] particularly residues involved in the binding pocket which will compromise translocase efficacy.[5]
MM is commonly associated with dysfunctional ATP/ADP translocase, but MM can be induced through many different mitochondrial abnormalities.

ATP/ADP translocase is very specifically inhibited by two families of inhibitors. The first family, which includes atractyloside (ATR) and carboxyatractyloside (CATR), binds to the ATP/ADP translocase from the matrix in lieu of ATP, causing eversion but keeping the translocase in the conformation facing the cytoplasm. In contrast, the second family, which includes

bongkrekic acid (BA) and isobongkrekic acid (isoBA), binds the translocase from the cytoplasmic side in lieu of ADP, causing eversion but keeping the translocase in the conformation facing the matrix.[17] The negatively-charged moieties of the inhibitors bind strongly with the positively-charged residues deep within the binding pocket. The high affinity (Kd in the nanomolar range) makes each inhibitor a deadly poison by obstructing cellular respiration/energy transfer to the rest of the cell.[4]

Further Reading

References

  1. ^
    ISBN 978-0-7167-8724-2.{{cite book}}: CS1 maint: multiple names: authors list (link
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  2. PMID 2990548.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link
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  3. ^
    PMID 3031073.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link
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  4. ^
    PMID 14603310.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link
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  5. ^
    PMID 8487299.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link
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  6. PMID 14392158.{{cite journal}}: CS1 maint: date and year (link
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  7. PMID 13549480.{{cite journal}}: CS1 maint: date and year (link
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  8. PMID 14151375.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link
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  9. PMID 5857365.{{cite journal}}: CS1 maint: date and year (link
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  10. PMID 5840415.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link
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  11. PMID 1259440. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: date and year (link
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  12. doi:10.1515/bchm2.1982.363.1.345.{{cite journal}}: CS1 maint: multiple names: authors list (link
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  13. PMID 3023860. {{cite journal}}: Check date values in: |date= (help)CS1 maint: multiple names: authors list (link
    )
  14. PMID 3050098. {{cite journal}}: Check date values in: |date= (help)CS1 maint: multiple names: authors list (link
    )
  15. PMID 9443707. {{cite journal}}: Check date values in: |date= (help
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  16. PMID 10926541.{{cite journal}}: CS1 maint: multiple names: authors list (link
    )
  17. PMID 12893834
    .


Category:Cellular respiration

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