Mitochondrial fatty acid synthesis and respiration

J. Kalervo Hiltunen, Kaija J. Autio, Melissa S. Schonauer, V. A Samuli Kursu, Carol L Dieckmann, Alexander J. Kastaniotis

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Recent studies have revealed that mitochondria are able to synthesize fatty acids in a malonyl-CoA/acyl carrier protein (ACP)-dependent manner. This pathway resembles bacterial fatty acid synthesis (FAS) type II, which uses discrete, nuclearly encoded proteins. Experimental evidence, obtained mainly through using yeast as a model system, indicates that this pathway is essential for mitochondrial respiratory function. Curiously, the deficiency in mitochondrial FAS cannot be complemented by inclusion of fatty acids in the culture medium or by products of the cytosolic FAS complex. Defects in mitochondrial FAS in yeast result in the inability to grow on nonfermentable carbon sources, the loss of mitochondrial cytochromes a/a3 and b, mitochondrial RNA processing defects, and loss of cellular lipoic acid. Eukaryotic FAS II generates octanoyl-ACP, a substrate for mitochondrial lipoic acid synthase. Endogenous lipoic acid synthesis challenges the hypothesis that lipoic acid can be provided as an exogenously supplied vitamin. Purified eukaryotic FAS II enzymes are catalytically active in vitro using substrates with an acyl chain length of up to 16 carbon atoms. However, with the exception of 3-hydroxymyristoyl-ACP, a component of respiratory complex I in higher eukaryotes, the fate of long-chain fatty acids synthesized by the mitochondrial FAS pathway remains an enigma. The linkage of FAS II genes to published animal models for human disease supports the hypothesis that mitochondrial FAS dysfunction leads to the development of disorders in mammals.

Original languageEnglish (US)
Pages (from-to)1195-1202
Number of pages8
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1797
Issue number6-7
DOIs
StatePublished - Jun 2010

Fingerprint

Respiration
Fatty Acids
Acyl Carrier Protein
Thioctic Acid
Yeast
Carbon
Yeasts
Malonyl Coenzyme A
Electron Transport Complex I
Animal Disease Models
Defects
Mitochondria
Cytochromes b
Mammals
Electron Transport Complex IV
Substrates
Eukaryota
Chain length
Vitamins
Byproducts

Keywords

  • Lipids
  • Lipoic acid
  • Metabolism
  • Mitochondria
  • Respiration
  • RNA processing

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology

Cite this

Hiltunen, J. K., Autio, K. J., Schonauer, M. S., Kursu, V. A. S., Dieckmann, C. L., & Kastaniotis, A. J. (2010). Mitochondrial fatty acid synthesis and respiration. Biochimica et Biophysica Acta - Bioenergetics, 1797(6-7), 1195-1202. https://doi.org/10.1016/j.bbabio.2010.03.006

Mitochondrial fatty acid synthesis and respiration. / Hiltunen, J. Kalervo; Autio, Kaija J.; Schonauer, Melissa S.; Kursu, V. A Samuli; Dieckmann, Carol L; Kastaniotis, Alexander J.

In: Biochimica et Biophysica Acta - Bioenergetics, Vol. 1797, No. 6-7, 06.2010, p. 1195-1202.

Research output: Contribution to journalArticle

Hiltunen, JK, Autio, KJ, Schonauer, MS, Kursu, VAS, Dieckmann, CL & Kastaniotis, AJ 2010, 'Mitochondrial fatty acid synthesis and respiration', Biochimica et Biophysica Acta - Bioenergetics, vol. 1797, no. 6-7, pp. 1195-1202. https://doi.org/10.1016/j.bbabio.2010.03.006
Hiltunen, J. Kalervo ; Autio, Kaija J. ; Schonauer, Melissa S. ; Kursu, V. A Samuli ; Dieckmann, Carol L ; Kastaniotis, Alexander J. / Mitochondrial fatty acid synthesis and respiration. In: Biochimica et Biophysica Acta - Bioenergetics. 2010 ; Vol. 1797, No. 6-7. pp. 1195-1202.
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