Mitochondrial lipid transport at a glance.

Lipids are the building blocks of cellular membranes and are synthesized at distinct parts of the cell. A precise control of lipid synthesis and distribution is crucial for cell function and survival. The endoplasmic reticulum (ER) is the major lipid-synthesizing organelle. However, a subset of lipids is synthesized within mitochondria, and this aspect has become a focus of recent lipid research. Mitochondria form a dynamic membrane network that is reshaped by fusion and fission events. Their functionality therefore depends on a continuous lipid supply from the ER and the distribution of lipids between both mitochondrial membranes. The mechanisms of mitochondrial lipid trafficking are only now emerging and appear to involve membrane contact sites and lipid transfer proteins. In this Cell Science at a Glance article, we will discuss recent discoveries in the field of mitochondrial lipid trafficking that build on long-standing observations and shed new light on the shuttling of membrane lipids between mitochondria and other organelles.

Screening for hydrolytic enzymes reveals Ayr1p as a novel triacylglycerol lipase in Saccharomyces cerevisiae.

Saccharomyces cerevisiae, as well as other eukaryotes, preserves fatty acids and sterols in a biologically inert form, as triacylglycerols and steryl esters. The major triacylglycerol lipases of the yeast S. cerevisiae identified so far are Tgl3p, Tgl4p, and Tgl5p (Athenstaedt, K., and Daum, G. (2003) YMR313c/TGL3 encodes a novel triacylglycerol lipase located in lipid particles of Saccharomyces cerevisiae. J. Biol. Chem. 278, 23317-23323; Athenstaedt, K., and Daum, G. (2005) Tgl4p and Tgl5p, two triacylglycerol lipases of the yeast Saccharomyces cerevisiae, are localized to lipid particles. J. Biol. Chem. 280, 37301-37309). We observed that upon cultivation on oleic acid, triacylglycerol mobilization did not come to a halt in a yeast strain deficient in all currently known triacylglycerol lipases, indicating the presence of additional not yet characterized lipases/esterases. Functional proteome analysis using lipase and esterase inhibitors revealed a subset of candidate genes for yet unknown hydrolytic enzymes on peroxisomes and lipid droplets. Based on the conserved GXSXG lipase motif, putative functions, and subcellular localizations, a selected number of candidates were characterized by enzyme assays in vitro, gene expression analysis, non-polar lipid analysis, and in vivo triacylglycerol mobilization assays. These investigations led to the identification of Ayr1p as a novel triacylglycerol lipase of yeast lipid droplets and confirmed the hydrolytic potential of the peroxisomal Lpx1p in vivo. Based on these results, we discuss a possible link between lipid storage, lipid mobilization, and peroxisomal utilization of fatty acids as a carbon source.

Mode of action of fluopyram in plant-parasitic nematodes.

Plant-parasitic nematodes (PPN) are responsible for severe yield losses in crop production. Management is challenging as effective and safe means are rare. Recently, it has been discovered that the succinate dehydrogenase (SDH) inhibitor fluopyram is highly effective against PPN while accompanying an excellent safety profile. Here we show that fluopyram is a potent inhibitor of SDH in nematodes but not in mammals, insects and earthworm, explaining the selectivity on molecular level. As a consequence of SDH inhibition, fluopyram impairs ATP generation and causes paralysis in PPN and Caenorhabditis elegans. Interestingly, efficacy differences of fluopyram amongst PPN species can be observed. Permanent exposure to micromolar to nanomolar amounts of fluopyram prevents Meloidogyne spp. and Heterodera schachtii infection and their development at the root. Preincubation of Meloidogyne incognita J2 with fluopyram followed by a recovery period effectively reduces gall formation. However, the same procedure does not inhibit H. schachtii infection and development. Sequence comparison of sites relevant for ligand binding identified amino acid differences in SDHC which likely mediate selectivity, coincidently revealing a unique amino acid difference within SDHC conserved among Heterodera spp. Docking and C. elegans mutant studies suggest that this minute difference mediates altered sensitivity of H. schachtii towards fluopyram.

Mitochondrial lipid trafficking.

Mitochondria are dynamic organelles surrounded by two membranes with a defined lipid composition. The majority of lipids are synthesized in the endoplasmic reticulum (ER) and transported to the mitochondria, but the synthesis of cardiolipin and phosphatidylethanolamine in the inner membrane of mitochondria highlights their general importance for cellular lipid metabolism. Extensive exchange of lipids and their precursors occurs between the ER and mitochondria as well as between mitochondrial membranes. The recent identification of membrane-tethering complexes and lipid-transfer proteins in mitochondria now provides the first insight into the mechanisms of these transport processes, which are of fundamental importance for mitochondrial activities and cell homeostasis. Here, we summarize the current understanding of lipid trafficking at the mitochondria and discuss emerging models for the mechanisms of lipid transfer.