3-Hydroxy-3-methylglutaryl coenzyme A lyase: Targeting and processing in peroxisomes and mitochondria

Lyudmila I. Ashmarina, Alexey V. Pshezhetsky, Steven S. Branda, Grazia Isaya, Grant A. Mitchell

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


3-Hydroxy-3-methylglutaryl coenzyme A lyase (HL, E.C. has a unique dual localization in both mitochondria and peroxisomes. Mitochondrial HL (~31.0 kDa) catalyzes the last step of ketogenesis; the function of peroxisomal HL (~33.5 kDa) is unknown. On density gradient fractionation, normal human lymphoblasts contain both peroxisomal and mitochondrial HL whereas in lymphoblasts from a patient with Zellweger syndrome, in which functional peroxisomes are absent, only the mitochondrial HL isoform was present. To study the kinetics of the dual targeting of HL, we performed pulse-chase experiments in normal and Zellweger cells. Pulse-chase studies revealed a biphasic curve for processing of the HL precursor. The first phase, with a calculated half-life of ~3 h in both normal and Zellweger fibroblasts and lymphoblasts and in HepG2 cells, presumably reflects mitochondrial import and processing of the precursor; the second (t(1/2), 12- 19 h) is present only in normal cells and presumably represents the half- life of peroxisomal HL. The half-life of mature mitochondrial HL was 14 to 19 h in both normal and Zellweger cells. Studies of the HMG-CoA lyase precursor in isolated rat mitochondria showed a rate of processing ~2.6-fold lower than that of the ornithine transcarbamylase precursor.

Original languageEnglish (US)
Pages (from-to)70-75
Number of pages6
JournalJournal of Lipid Research
Issue number1
StatePublished - Jan 1999


  • Amino acid metabolism
  • Hydroxymethylglutaryl CoA
  • Inborn errors
  • Ketoacid lyases
  • Ketone bodies
  • Mitochondria
  • Peroxisomes

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology


Dive into the research topics of '3-Hydroxy-3-methylglutaryl coenzyme A lyase: Targeting and processing in peroxisomes and mitochondria'. Together they form a unique fingerprint.

Cite this