Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Apr 3;284(14):9011-5.
doi: 10.1074/jbc.R800068200. Epub 2008 Nov 21.

Mitochondrial fatty acid synthesis type II: more than just fatty acids

J Kalervo Hiltunen  1 , Melissa S Schonauer, Kaija J Autio, Telsa M Mittelmeier, Alexander J Kastaniotis, Carol L Dieckmann
Affiliations
Review

Mitochondrial fatty acid synthesis type II: more than just fatty acids

J Kalervo Hiltunen et al. J Biol Chem. .

Abstract

Eukaryotes harbor a highly conserved mitochondrial pathway for fatty acid synthesis (FAS), which is completely independent of the eukaryotic cytosolic FAS apparatus. The activities of the mitochondrial FAS system are catalyzed by soluble enzymes, and the pathway thus resembles its prokaryotic counterparts. Except for octanoic acid, which is the direct precursor for lipoic acid synthesis, other end products and functions of the mitochondrial FAS pathway are still largely enigmatic. In addition to low cellular levels of lipoic acid, disruption of genes encoding mitochondrial FAS enzymes in yeast results in a respiratory-deficient phenotype and small rudimentary mitochondria. Recently, two distinct links between mitochondrial FAS and RNA processing have been discovered in vertebrates and yeast, respectively. In vertebrates, the mitochondrial 3-hydroxyacyl-acyl carrier protein dehydratase and the RPP14 subunit of RNase P are encoded by the same bicistronic transcript in an evolutionarily conserved arrangement that is unusual for eukaryotes. In yeast, defects in mitochondrial FAS result in inefficient RNase P cleavage in the organelle. The intersection of mitochondrial FAS and RNA metabolism in both systems provides a novel mechanism for the coordination of intermediary metabolism in eukaryotic cells.

PubMed Disclaimer

Figures

FIGURE 1.
FIGURE 1.
Reactions and proteins of the mitochondrial FAS pathway. A, individual reactions of the FAS II pathway. As discussed in text, it remains to be experimentally demonstrated that generation of acyl-ACP exceeds a chain length of C8 in vivo and that longer fatty acids have a role in mitochondrial physiology. B, protein components of the mitochondrial FAS pathway and the corresponding genes in yeast and humans. All proteins of the mitochondrial FAS pathway required to synthesize saturated fatty acids have been identified and at least partially characterized in bakers' yeast. The enzymes responsible for carboxylation of acetyl-CoA and the 3-ketoacyl-ACP reduction reaction in humans have not yet been determined.
FIGURE 2.
FIGURE 2.
Metabolic fluxes and functional links associated with the mitochondrial FAS type II pathway in yeast. Solid arrows represent metabolic fluxes, and dashed arrows indicate functional links. The large arrow indicates that an unidentified product of fatty acid or lipoic acid synthesis or a derivative thereof affects the efficiency of RNase P processing of the RPM1-tRNAPro precursor RNA. Alternative sources of acetyl-CoA other than that generated by PDH (pyruvate bypass, amino acid breakdown, or transfer of extramitochondrially produced acetyl units) have been omitted for clarity. FAs, fatty acids; α-KDH, α-ketoglutarate dehydrogenase.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. White, S. W., Zheng, J., Zhang, Y. M., and Rock, C.O. (2005) Annu. Rev. Biochem. 74 791–831 - PubMed
    1. Burger, G., Gray, M. W., and Lang, B. F. (2003) Trends Genet. 19 709–716 - PubMed
    1. Clayton, D. A. (1984) Annu. Rev. Biochem. 53 573–594 - PubMed
    1. Schafer, B. (2005) Gene (Amst.) 354 80–85 - PubMed
    1. Dieckmann, C. L., and Staples, R. R. (1994) Int. Rev. Cytol. 152 145–181 - PubMed

Publication types