Programmed death (apoptosis) is turned on in damaged or unwanted cells to secure their clean and safe self-elimination. The initial apoptotic events are coordinated in mitochondria, whereby several ...proapoptotic factors, including cytochrome c, are released into the cytosol to trigger caspase cascades. The release mechanisms include interactions of B-cell/lymphoma 2 family proteins with a mitochondria-specific phospholipid, cardiolipin, to cause permeabilization of the outer mitochondrial membrane. Using oxidative lipidomics, we showed that cardiolipin is the only phospholipid in mitochondria that undergoes early oxidation during apoptosis. The oxidation is catalyzed by a cardiolipin-specific peroxidase activity of cardiolipin-bound cytochrome c. In a previously undescribed step in apoptosis, we showed that oxidized cardiolipin is required for the release of proapoptotic factors. These results provide insight into the role of reactive oxygen species in triggering the cell-death pathway and describe an early role for cytochrome c before caspase activation.
Lutetium orthotantalate with M′-fergusonite type structure was synthesized using a reverse coprecipitation method. Phase and chemical composition, as well as microstructure of the synthesized sample, ...were characterized by X-ray diffraction (XRD), μ-X-ray fluorescence and Fourier-transform infrared spectroscopies, and scanning electron microscopy. Heat capacity of M′-LuTaO4 was first studied by adiabatic and differential scanning calorimetry (DSC) in the temperature range from 10 to 1300 K. Using a temperature dependence of heat capacity, the standard thermodynamic functions (entropy Smo(T), enthalpy change Hmo(T)–Hmo(0) and derived Gibbs energy Фmo(T)) were calculated in the range of T→0–1300 K. The standard molar entropy of M′-LuTaO4 at 298.15 K is 123.12 ± 0.50 J K−1 mol−1. A comparison of the experimental heat capacity values, obtained by DSC, with those calculated using the empirical Neumann-Kopp rule showed a reasonable agreement between the two sets of data only up to ≈1000 K. The high-temperature evolution of the lattice parameters for M′-LuTaO4 was studied by high-temperature XRD (HTXRD). According to the high-temperature heat capacity study and the HTXRD measurements, there were no phase transformations up to 1300 K. Based on the HTXRD data, the linear and volume thermal expansion coefficients were obtained for the first time.
Recently, phospholipid peroxidation products gained a reputation as key regulatory molecules and participants in oxidative signaling pathways. During apoptosis, a mitochondria-specific phospholipid, ...cardiolipin (CL), interacts with cytochrome
c (cyt
c) to form a peroxidase complex that catalyzes CL oxidation; this process plays a pivotal role in the mitochondrial stage of the execution of the cell death program. This review is focused on redox mechanisms and essential structural features of cyt
c’s conversion into a CL-specific peroxidase that represent an interesting and maybe still unique example of a functionally significant ligand change in hemoproteins. Furthermore, specific characteristics of CL in mitochondria—its asymmetric transmembrane distribution and mechanisms of collapse, the regulation of its synthesis, remodeling, and fatty acid composition—are given significant consideration. Finally, new concepts in drug discovery based on the design of mitochondria-targeted inhibitors of cyt
c/CL peroxidase and CL peroxidation with antiapoptotic effects are presented.
Recognition of injured mitochondria for degradation by macroautophagy is essential for cellular health, but the mechanisms remain poorly understood. Cardiolipin is an inner mitochondrial membrane ...phospholipid. We found that rotenone, staurosporine, 6-hydroxydopamine and other pro-mitophagy stimuli caused externalization of cardiolipin to the mitochondrial surface in primary cortical neurons and SH-SY5Y cells. RNAi knockdown of cardiolipin synthase or of phospholipid scramblase-3, which transports cardiolipin to the outer mitochondrial membrane, decreased the delivery of mitochondria to autophagosomes. Furthermore, we found that the autophagy protein microtubule-associated-protein-1 light chain 3 (LC3), which mediates both autophagosome formation and cargo recognition, contains cardiolipin-binding sites important for the engulfment of mitochondria by the autophagic system. Mutation of LC3 residues predicted as cardiolipin-interaction sites by computational modelling inhibited its participation in mitophagy. These data indicate that redistribution of cardiolipin serves as an 'eat-me' signal for the elimination of damaged mitochondria from neuronal cells.
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