Mitochondrial trifunctional protein defects: Clinical implications and therapeutic approaches

R. Scott Rector, R. Mark Payne, Jamal A. Ibdah

Research output: Contribution to journalReview article

34 Scopus citations

Abstract

The mitochondrial trifunctional protein (MTP) is a heterotrimeric protein that consists of four α-subunits and four β-subunits and catalyzes three of the four chain-shortening reactions in the mitochondrial β-oxidation of long-chain fatty acids. Families with recessively inherited MTP defects display a spectrum of maternal and fetal phenotypes. Current management of patients with MTP defects include long-term dietary therapy of fasting avoidance, low-fat/high-carbohydrate diet with restriction of long-chain fatty acid intake and substitution with medium-chain fatty acids. These dietary approaches appear promising in the short-term, but the long-term outcome of patients treated with dietary intervention is largely unknown. Potential therapeutic approaches targeted at correcting the metabolic defect will be discussed. We will discuss the potential use of protein transduction domains that cross the mitochondrial membranes for the treatment of mitochondrial disorders. In addition, we discuss the phenotypes of MTP in a heterozygous state and potential ways to intervene to increase hepatic fatty acid oxidative capacity.

Original languageEnglish (US)
Pages (from-to)1488-1496
Number of pages9
JournalAdvanced Drug Delivery Reviews
Volume60
Issue number13-14
DOIs
StatePublished - Oct 1 2008

Keywords

  • β-oxidation
  • Cell penetrant peptide
  • Fatty acids
  • Fusion proteins
  • LCHAD
  • Mitochondria
  • Mitochondrial trifunctional protein
  • Protein transduction domain
  • PTD
  • TAT

ASJC Scopus subject areas

  • Pharmaceutical Science

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