mitochondrial trifunctional protein

Fatty acid beta-oxidation (FAO) and oxidative phosphorylation (OXPHOS) are two major metabolic pathways in the mitochondria. Reducing equivalents from FAO enter OXPHOS at the level of complexes I and III. In 2010, Wang et al. discovered a functional and physical association between MTP and ETC respirasomes. Not only does MTP appear to be bound to Complex I, but it also appears to channel substrates between the two enzymes.{{cite journal|last1=Wang|first1=Y.|last2=Mohsen|first2=A.-W.|last3=Mihalik|first3=S. J.|last4=Goetzman|first4=E. S.|last5=Vockley|first5=J.|title=Evidence for Physical Association of Mitochondrial Fatty Acid Oxidation and Oxidative Phosphorylation Complexes|journal=Journal of Biological Chemistry|volume=285|issue=39|year=2010|pages=29834–29841|issn=0021-9258|doi=10.1074/jbc.M110.139493|pmid=20663895|pmc=2943265|doi-access=free}} This is especially interesting, because up until then it was unknown exactly how MTP was associated with the inner mitochondrial membrane, and this discovery may provide the explanation.

Recent research has revealed that MTP can be affected by various hormones, via hormone receptors located in the mitochondria. Chochron et al. (2012) demonstrated that thyroid hormone stimulates mitochondrial metabolism in a pathway mediated by MTP.{{cite journal|last1=Chocron|first1=E. S.|last2=Sayre|first2=N. L.|last3=Holstein|first3=D.|last4=Saelim|first4=N.|last5=Ibdah|first5=J. A.|last6=Dong|first6=L. Q.|last7=Zhu|first7=X.|last8=Cheng|first8=S.-Y.|last9=Lechleiter|first9=J. D.|title=The Trifunctional Protein Mediates Thyroid Hormone Receptor-Dependent Stimulation of Mitochondria Metabolism|journal=Molecular Endocrinology|volume=26|issue=7|year=2012|pages=1117–1128|issn=0888-8809|doi=10.1210/me.2011-1348|pmid=22570332|pmc=3385793}} Zhou et al. (2012) used 2D gel electrophoresis and mass spectrometry to identify MTP as one of the proteins that interacts with ER alpha, a receptor triggered by estrogen.{{cite journal|last1=Zhou|first1=Z.|last2=Zhou|first2=J.|last3=Du|first3=Y.|title=Estrogen Receptor Alpha Interacts with Mitochondrial Protein HADHB and Affects Beta-Oxidation Activity|journal=Molecular & Cellular Proteomics|volume=11|issue=7|year=2012|pages=M111.011056|issn=1535-9476|doi=10.1074/mcp.M111.011056|doi-access=free |pmid=22375075|pmc=3394935}}

In 2009, Taylor et al. identified a human mitochondrial protein, monolysocardiolipin acyltransferase (MLCL AT-1), that is identical in amino acid sequence to the 59-kDa C-terminal end of MTP, linking MTP to the remodeling of cardiolipin from monolysocardiolipin.{{cite journal|last1=Taylor|first1=W. A.|last2=Hatch|first2=G. M.|title=Identification of the Human Mitochondrial Linoleoyl-coenzyme A Monolysocardiolipin Acyltransferase (MLCL AT-1)|journal=Journal of Biological Chemistry|volume=284|issue=44|year=2009|pages=30360–30371|issn=0021-9258|doi=10.1074/jbc.M109.048322|pmid=19737925|pmc=2781591|doi-access=free}} Although MLCL AT-1 and MTP are different proteins, in 2012 the same lab discovered that MTP did indeed have cardiolipin remodeling capabilities.{{cite journal|last1=Beh|first1=Christopher|last2=Taylor|first2=William A.|last3=Mejia|first3=Edgard M.|last4=Mitchell|first4=Ryan W.|last5=Choy|first5=Patrick C.|last6=Sparagna|first6=Genevieve C.|last7=Hatch|first7=Grant M.|title=Human Trifunctional Protein Alpha Links Cardiolipin Remodeling to Beta-Oxidation|journal=PLOS ONE|volume=7|issue=11|year=2012|pages=e48628|issn=1932-6203|doi=10.1371/journal.pone.0048628|pmid=23152787|pmc=3494688|bibcode=2012PLoSO...748628T|doi-access=free}} This suggests a possible link between mitochondrial membrane cardiolipin content and beta oxidation.

Disorders associated with MTP are:{{citation needed|date=May 2024}}

• Mitochondrial trifunctional protein deficiency
• LCHAD deficiency
• Acute fatty liver of pregnancy

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• {{MeshName|mitochondrial+trifunctional+protein+TP}}

{{Multienzyme complexes}}

{{Lipid metabolism enzymes}}

{{Mitochondrial enzymes}}

Category:Proteins