Functional analysis of mutations in the human carnitine/acylcarnitine translocase in Aspergillus nidulans

Pérez, Patricia Vázquez; Martı́nez, Óscar; Romero, Beatriz; Olivas, Israel; Pedregosa, Ana; Palmieri, Ferdinando; Laborda, F.; Lucas, J. Ramón De

doi:10.1016/s1087-1845(03)00049-5

Cited by 16 publications

(30 citation statements)

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“…Short-chain fatty acids can in fact enter the mitochondria via a still unknown mechanism independently of the CAC. The numerous mutations found in the patients' CAC gene (SLC25A20) [63] cause loss of transport activity, as shown by transport assays in the reconstituted system and by complementation of S. cerevisiae or Aspergillus nidulans deleted strains (see [64] and references therein). In some patients, coding sequence mutations have been shown to increase the amount of aberrant mRNA splicing and exon skipping, causing absence of normal transcripts.…”

Section: Graves' Disease Carrier Gdc (Slc25a16)mentioning

confidence: 99%

The mitochondrial transporter family (SLC25): physiological and pathological implications

Palmieri

2004

Pfl�gers Archiv European Journal of Physiology

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The mitochondrial carriers (MCs) shuttle a variety of metabolites across the inner mitochondrial membrane (i.m.m.). In man they are encoded by the SLC25 genes. Some MCs have isoforms encoded by different SLC25 genes, whereas the phosphate carrier has two variants arising from an alternative splicing of SLC25A3. Six MCs have been sequenced after purification, and many more have been identified from their transport and kinetic properties following heterologous over-expression and reconstitution into liposomes. All MCs of known function belong to the same protein family, since their polypeptide chains consist of three tandemly related sequences of about 100 amino acids, and the repeats of the different carriers are homologous. They probably function as homodimers, each monomer being folded in the membrane into six transmembrane segments. The functional information obtained in studies with mitochondria and/or the reconstituted system has helped to gain an insight into the physiological role of the MCs in cell metabolism, as have tissue distribution, the use of knock-out mice (and/or yeast) and over-expression in human cell lines (or yeast) of individual carriers and isoforms. At the same time, the cloning and functional identification of many SLC25 genes has made it possible (i) to identify the genes (and their defects) responsible for some diseases, e.g. Stanley syndrome and Amish microcephaly, and (ii) where the genes were already known, to characterize the function of the gene products and hence understand the molecular basis and the symptoms of the diseases, e.g. hyperornithinaemia, hyperammonaemia and homocitrullinuria (HHH) syndrome and type II citrullinemia. It is likely that further extension and functional characterization of the SLC25 gene family will elucidate other diseases caused by MC deficiency.

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Section: Graves' Disease Carrier Gdc (Slc25a16)mentioning

confidence: 99%

The mitochondrial transporter family (SLC25): physiological and pathological implications

Palmieri

2004

Pfl�gers Archiv European Journal of Physiology

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691

576

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“…C2-metabolism and gluconeogenesis 3.5.1. Catabolism of ethanol and acetate By the virtue of classical genetics, ethanol and acetate catabolism and their conversion to glucose is relatively well understood in A. nidulans (see, e.g., Apirion, 1965;Skinner and Armitt, 1972;Armitt et al, 1976;Midgley, 1993;Felenbok et al, 2001;Pérez et al, 2003;Hynes et al, 2007). Almost all corresponding genesalcA, alcR, and aldA (ethanol conversion); facA, facB, and facC (acetate activation); acuD and acuE (glyoxylate cycle); pycA (pyruvate carboxylase), acuF, acuG, acuH, acuJ, acuK, and acuM (gluconeogenesis)-were annotated (Table 6).…”

Section: Side Reactions With Tca Cycle Intermediatesmentioning

confidence: 99%

Biodiversity and evolution of primary carbon metabolism in Aspergillus nidulans and other Aspergillus spp.

Flipphi¹,

Sun²,

Robellet³

et al. 2009

Fungal Genetics and Biology

102

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“…Although the MoCrc1-GFP protein in conidia was unevenly distributed, we could not accurately determine the sub-cellular localization of this protein. Previously, the homologous proteins of MoCrc1 have been documented as a mitochondrial protein in other species, including A. nidulans, A. thaliana, D. melanogaster, and S. cerevisiae (De Lucas et al 2001;Hartenstein et al 1997;Lawand et al 2002;Palmieri et al 1999;Perez et al 2003). Based on this, it is likely that MoCrc1 is also a mitochondrial protein in M. oryzae.…”

Section: Discussionmentioning

confidence: 98%

“…Growth of the DMocrc1 null mutant was severely reduced on minimal medium with sodium acetate or olive oil (0 hpi), appressoria (12 hpi), and infectious hyphae (36 hpi) were examined and photographed with differential interference contrast (DIC) and epifluorescence (eGFP) microscopy. Bar 20 lm AcuH in A. nidulans (De Lucas et al 1999;Perez et al 2003), MoCrc1 was required for utilization of C2 compounds, like acetate, and fatty acids, like olive oil. This is consistent with MoCrc1 being a putative carnitineacylcarnitine carrier protein.…”

Section: Discussionmentioning

confidence: 99%

“…In the budding yeast Saccharomyces cerevisiae, mutation of the carnitine-acylcarnitine carrier protein, Crc1, prevented growth on media containing oleate when the citrate synthase locus was also deleted (van Roermund et al 1999). Different from Crc1, the carnitine-acylcarnitine carrier protein, AcuH, of the fungus Aspergillus nidulans was essential for growth on ketogenic compounds, such as C 2 compounds (acetate) and fatty acids (De Lucas et al 1999;Perez et al 2003). Thus far, however, the roles of carnitine-acylcarnitine carrier proteins in plant pathogenic fungi have not been reported.…”

Section: Introductionmentioning

confidence: 99%

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A carnitine–acylcarnitine carrier protein, MoCrc1, is essential for pathogenicity in Magnaporthe oryzae

et al. 2012

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The rice blast fungus Magnaporthe oryzae forms a specialized infection structure called an appressorium to breach the host-plant epidermis for successful infection. In this study, a mutant defective in appressorial penetration was isolated by a mutagenesis approach, in which an exogenous DNA fragment was found to be inserted into the first exon of MoCRC1. This gene encodes a putative carnitine-acylcarnitine carrier protein that is widely conserved among eukaryotic organisms. Deletion of MoCRC1 severely reduces appressorium turgor generation, appressorial penetration, and development of infection hyphae. The null mutant of MoCRC1 lost pathogenicity on intact and abraded host leaves. MoCRC1 was also found to be required for growth on minimal medium containing sodium acetate or olive oil. Moreover, the transformed MoCrc1-eGFP fusion protein was expressed throughout the infection process. Our results suggest that the carnitine-acylcarnitine carrier protein plays vital roles in appressorium-mediated infection and is essential for pathogenesis of M. oryzae and perhaps other phytopathogenic fungi.

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Functional analysis of mutations in the human carnitine/acylcarnitine translocase in Aspergillus nidulans

Cited by 16 publications

References 35 publications

The mitochondrial transporter family (SLC25): physiological and pathological implications

The mitochondrial transporter family (SLC25): physiological and pathological implications

Biodiversity and evolution of primary carbon metabolism in Aspergillus nidulans and other Aspergillus spp.

A carnitine–acylcarnitine carrier protein, MoCrc1, is essential for pathogenicity in Magnaporthe oryzae

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