ORCID Profile
0000-0003-2083-3002
Current Organisations
UGA-CNRS
,
CNRS Délégation Alpes
,
Université Grenoble Alpes
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Springer Science and Business Media LLC
Date: 17-05-2021
DOI: 10.1038/S41467-021-22956-W
Abstract: Apicomplexa are obligate intracellular parasites responsible for major human diseases. Their intracellular survival relies on intense lipid synthesis, which fuels membrane biogenesis. Parasite lipids are generated as an essential combination of fatty acids scavenged from the host and de novo synthesized within the parasite apicoplast. The molecular and metabolic mechanisms allowing regulation and channeling of these fatty acid fluxes for intracellular parasite survival are currently unknown. Here, we identify an essential phosphatidic acid phosphatase in Toxoplasma gondii , Tg LIPIN, as the central metabolic nexus responsible for controlled lipid synthesis sustaining parasite development. Lipidomics reveal that Tg LIPIN controls the synthesis of diacylglycerol and levels of phosphatidic acid that regulates the fine balance of lipids between storage and membrane biogenesis. Using fluxomic approaches, we uncover the first parasite host-scavenged lipidome and show that Tg LIPIN prevents parasite death by ‘lipotoxicity’ through effective channeling of host-scavenged fatty acids to storage triacylglycerols and membrane phospholipids.
Publisher: American Society for Microbiology
Date: 08-2008
DOI: 10.1128/EC.00132-08
Abstract: The twin-Cx 9 C motif protein Pet191 is essential for cytochrome c oxidase maturation. The motif Cys residues are functionally important and appear to be present in disulfide linkages within a large oligomeric complex associated with the mitochondrial inner membrane. The import of Pet191 differs from that of other twin-Cx 9 C motif class of proteins in being independent of the Mia40 pathway.
Publisher: Elsevier BV
Date: 05-2006
Publisher: Elsevier BV
Date: 12-2006
Publisher: Elsevier BV
Date: 07-2006
DOI: 10.1016/J.BBAMCR.2006.03.002
Abstract: Copper is required within the mitochondrion for the function of two metalloenzymes, cytochrome c oxidase (CcO) and superoxide dismutase (Sod1). Copper metallation of these two enzymes occurs within the mitochondrial intermembrane space and is mediated by metallochaperone proteins. Cox17 is a key copper donor to two accessory proteins, Sco1 and Cox11, to form the two copper centers in the mature CcO complex. Ccs1 is the necessary metallochaperone for the copper metallation of Sod1 in the IMS as well as within the cytoplasm where the bulk of Sod1 resides. Copper ions used in the metallation of CcO and Sod1 appear to be provided by a novel copper pool within the mitochondrial matrix. This review documents copper ion shuttling within the mitochondrion and the proteins that mediate assembly of active CcO and Sod1.
Publisher: Informa UK Limited
Date: 08-2008
DOI: 10.1128/MCB.00057-08
Publisher: Springer Science and Business Media LLC
Date: 13-10-2022
DOI: 10.1038/S41467-022-33641-X
Abstract: Overexposure to manganese disrupts cellular energy metabolism across species, but the molecular mechanism underlying manganese toxicity remains enigmatic. Here, we report that excess cellular manganese selectively disrupts coenzyme Q (CoQ) biosynthesis, resulting in failure of mitochondrial bioenergetics. While respiratory chain complexes remain intact, the lack of CoQ as lipophilic electron carrier precludes oxidative phosphorylation and leads to premature cell and organismal death. At a molecular level, manganese overload causes mismetallation and proteolytic degradation of Coq7, a diiron hydroxylase that catalyzes the penultimate step in CoQ biosynthesis. Coq7 overexpression or supplementation with a CoQ headgroup analog that bypasses Coq7 function fully corrects electron transport, thus restoring respiration and viability. We uncover a unique sensitivity of a diiron enzyme to mismetallation and define the molecular mechanism for manganese-induced bioenergetic failure that is conserved across species.
Publisher: Wiley
Date: 20-09-2007
Publisher: Springer Science and Business Media LLC
Date: 16-01-2007
DOI: 10.1007/S10534-006-9052-9
Abstract: Transition metal ions are required for many aspects of mitochondrial physiology. Copper, iron, manganese and zinc are cofactors in metalloenzymes and metalloproteins within the organelle. Little is known how cells maintain optimal pools of these metal ions for mitochondrial function. This review documents the available literature on mitochondrial metal ion pools and protein metallation reactions. Upon perturbation in metal pools, mis-metallation reactions do occur. Thus, regulation of metal ion accessibility and bioavailability must exist.
No related grants have been discovered for Fabien Pierrel.