Mitochondrial fatty acid synthesis: a relic of endosymbiontic origin and a specialized means for respiration

Schneider, Ralf; Brors, Benedikt; Massow, Michael; Weiss, Hanns

doi:10.1016/s0014-5793(97)00360-8

Cited by 64 publications

(33 citation statements)

References 43 publications

(54 reference statements)

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“…Mitochondria have been demonstrated to possess all the enzymes involved in de novo FA synthesis and can synthesize long-chain acyl-ACP independently (Gueguen et al, 2000;Focke et al, 2003). The functions of mitochondrial FA synthesis in organisms with type I FA synthesis, such as Saccharomyces cerevisiae and Caenorhabditis elegans, have been demonstrated to provide ACP-bound FAs as substrates for the repair of mitochondrial phospholipids and for covalent modification of respiratory complex subunits (Schneider et al, 1997;Lange et al, 2001). In plants (organisms with type II FA synthesis), mitochondrial FA synthesis provides substrates for lipoic acid synthesis; this is a sulfur-containing cofactor involved in several multienzyme complexes, such as pyruvate dehydrogenases and Gly decarboxylases (Wada et al, 1997;Gueguen et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Arabidopsis β-Ketoacyl-[Acyl Carrier Protein] Synthase I Is Crucial for Fatty Acid Synthesis and Plays a Role in Chloroplast Division and Embryo Development

2010

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Lipid metabolism plays a pivotal role in cell structure and in multiple plant developmental processes. b-Ketoacyl-[acyl carrier protein] synthase I (KASI) catalyzes the elongation of de novo fatty acid (FA) synthesis. Here, we report the functional characterization of KASI in the regulation of chloroplast division and embryo development. Phenotypic observation of an Arabidopsis thaliana T-DNA insertion mutant, kasI, revealed multiple morphological defects, including chlorotic (in netted patches) and curly leaves, reduced fertility, and semidwarfism. There are only one to five enlarged chloroplasts in the mesophyll cells of chlorotic sectors of young kasI rosette leaves, indicating suppressed chloroplast division under KASI deficiency. KASI deficiency results in a significant change in the polar lipid composition, which causes the suppressed expression of FtsZ and Min system genes, disordered Z-ring placement in the oversized chloroplast, and inhibited polymerization of FtsZ protein at mid-site of the chloroplast in kasI. In addition, KASI deficiency results in disrupted embryo development before the globular stage and dramatically reduces FA levels (;33.6% of the wild type) in seeds. These results demonstrate that de novo FA synthesis is crucial and has pleiotropic effects on plant growth. The polar lipid supply is important for chloroplast division and development, revealing a key function of FA synthesis in plastid development.

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Section: Discussionmentioning

confidence: 99%

Arabidopsis β-Ketoacyl-[Acyl Carrier Protein] Synthase I Is Crucial for Fatty Acid Synthesis and Plays a Role in Chloroplast Division and Embryo Development

2010

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“…The FAS II pathway may play a role in the maintenance of mitochondrial morphology as deletion or overexpression of genes encoding pathway enzymes causes morphological defects (25,53). It has also been suggested that the FAS II pathway may provide fatty acids for phospholipid repair (42) or for insertion of membrane proteins (19), but no evidence has been generated to support these hypotheses. While it has been shown for other organisms that the mitochondrial FAS II pathway is capable of synthesis of fatty acids longer than C8 (60), the physiological relevance of these fatty acids still remains to be demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Intersection of RNA Processing and the Type II Fatty Acid Synthesis Pathway in Yeast Mitochondria

Schonauer

Kastaniotis

Hiltunen

et al. 2008

Molecular and Cellular Biology

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Distinct metabolic pathways can intersect in ways that allow hierarchical or reciprocal regulation. In a screen of respiration-deficient Saccharomyces cerevisiae gene deletion strains for defects in mitochondrial RNA processing, we found that lack of any enzyme in the mitochondrial fatty acid type II biosynthetic pathway (FAS II) led to inefficient 5 processing of mitochondrial precursor tRNAs by RNase P. In particular, the precursor containing both RNase P RNA (RPM1) and tRNA Pro accumulated dramatically. Subsequent Pet127-driven 5 processing of RPM1 was blocked. The FAS II pathway defects resulted in the loss of lipoic acid attachment to subunits of three key mitochondrial enzymes, which suggests that the octanoic acid produced by the pathway is the sole precursor for lipoic acid synthesis and attachment. The protein component of yeast mitochondrial RNase P, Rpm2, is not modified by lipoic acid in the wild-type strain, and it is imported in FAS II mutant strains. Thus, a product of the FAS II pathway is required for RNase P RNA maturation, which positively affects RNase P activity. In addition, a product is required for lipoic acid production, which is needed for the activity of pyruvate dehydrogenase, which feeds acetyl-coenzyme A into the FAS II pathway. These two positive feedback cycles may provide switch-like control of mitochondrial gene expression in response to the metabolic state of the cell.Intersections of biological pathways previously thought to be distinct have emerged recently from genome-wide functional screens in model organisms (52,62,63). Through a genomewide screen of Saccharomyces cerevisiae, we have discovered the intersection of mitochondrial type II fatty acid synthesis (FAS II) with mitochondrial RNA processing.There are two distinct fatty acid synthesis pathways in eukaryotes. Fatty acid synthesis type I (FAS I) is catalyzed by cytosolic multifunctional enzyme complexes that produce the bulk of fatty acids in the cell (45). FAS II occurs in mitochondria and chloroplasts (as well as in prokaryotes) and is catalyzed by the sequential action of individual enzymes (21, 51). The mitochondrial FAS II pathway produces octanoic acid, which is the precursor molecule for the synthesis of lipoic acid. Lipoic acid is the "swinging arm" cofactor that serves to shuttle reaction intermediates between the active sites of several mitochondrial keto acid dehydrogenase complexes (35). In yeast, lipoic acid is covalently bound to conserved lysine residues on three different proteins, the E2 subunit of pyruvate dehydrogenase (PDH) (34) and ␣-ketoglutarate dehydrogenase (␣-KDH) (38) and on the H protein of the glycine cleavage enzyme (GC) (33).Mitochondrial genes are expressed through a coordinated effort between the nuclear and the mitochondrial genomes. Mitochondrial DNA in eukaryotes encodes a small number of proteins that are components of the respiratory chain complexes and ATP synthase, as well as mitochondrial rRNAs and most tRNAs (1, 15). Other proteins required for mitochondrial function are encod...

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“…Although the cytosolic ACP and fatty acid synthetase complex have been characterized as the major proteins involved in fatty acid synthesis, a mitochondrial ACP protein distinct from cytosolic ACP has also been identified and shown to contain a phosphopantetheine prosthetic group (Sackmann et al, 1991;Zhang et al, 2003). The precise role of a separate mitochondrial pathway for fatty acid synthesis is not yet clear, but there is evidence in fungal systems that it may be essential for maintenance of phospholipids of the mitochondrial membranes (Schneider et al, 1995(Schneider et al, , 1997. Alternatively, other fatty acyl CoA derivatives may be important products of this pathway.…”

Section: Discussionmentioning

confidence: 99%

Altered Neuronal Mitochondrial Coenzyme A Synthesis in Neurodegeneration with Brain Iron Accumulation Caused by Abnormal Processing, Stability, and Catalytic Activity of Mutant Pantothenate Kinase 2

Kotzbauer¹,

Truax²,

Trojanowski³

et al. 2005

J. Neurosci.

133

126

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Mutations in the pantothenate kinase 2 (PANK2) gene have been identified in patients with neurodegeneration with brain iron accumulation (NBIA; formerly Hallervorden-Spatz disease). However, the mechanisms by which these mutations cause neurodegeneration are unclear, especially given the existence of multiple pantothenate kinase genes in humans and multiple PanK2 transcripts with potentially different subcellular localizations. We demonstrate that PanK2 protein is localized to mitochondria of neurons in human brain, distinguishing it from other pantothenate kinases that do not possess mitochondrial-targeting sequences. PanK2 protein translated from the most 5Ј start site is sequentially cleaved at two sites by the mitochondrial processing peptidase, generating a long-lived 48 kDa mature protein identical to that found in human brain extracts. The mature protein catalyzes the initial step in coenzyme A (CoA) synthesis but displays feedback inhibition in response to species of acyl CoA rather than CoA itself. Some, but not all disease-associated point mutations result in significantly reduced catalytic activity. The most common mutation, G521R, results in marked instability of the intermediate PanK2 isoform and reduced production of the mature isoform. These results suggest that NBIA is caused by altered neuronal mitochondrial lipid metabolism caused by mutations disrupting PanK2 protein levels and catalytic activity.

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Mitochondrial fatty acid synthesis: a relic of endosymbiontic origin and a specialized means for respiration

Cited by 64 publications

References 43 publications

Arabidopsis β-Ketoacyl-[Acyl Carrier Protein] Synthase I Is Crucial for Fatty Acid Synthesis and Plays a Role in Chloroplast Division and Embryo Development

Arabidopsis β-Ketoacyl-[Acyl Carrier Protein] Synthase I Is Crucial for Fatty Acid Synthesis and Plays a Role in Chloroplast Division and Embryo Development

Intersection of RNA Processing and the Type II Fatty Acid Synthesis Pathway in Yeast Mitochondria

Altered Neuronal Mitochondrial Coenzyme A Synthesis in Neurodegeneration with Brain Iron Accumulation Caused by Abnormal Processing, Stability, and Catalytic Activity of Mutant Pantothenate Kinase 2

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