The Targeting of Plasmalemmal Ceramide to Mitochondria during Apoptosis

Ceramide is a key lipid mediator of cellular processes such as differentiation, proliferation, growth arrest and apoptosis. During apoptosis, ceramide is produced within the plasma membrane. Although recent data suggest that the generation of intracellular ceramide increases mitochondrial permeability, the source of mitochondrial ceramide remains unknown. Here, we determine whether a stress-mediated plasmalemmal pool of ceramide might become available to the mitochondria of apoptotic cells. We have previously established annexin A1—a member of a family of Ca2+ and membrane-binding proteins—to be a marker of ceramide platforms. Using fluorescently tagged annexin A1, we show that, upon its generation within the plasma membrane, ceramide self-associates into platforms that subsequently invaginate and fuse with mitochondria. An accumulation of ceramide within the mitochondria of apoptotic cells was also confirmed using a ceramide-specific antibody. Electron microscopic tomography confirmed that upon the formation of ceramide platforms, the invaginated regions of the plasma membrane extend deep into the cytoplasm forming direct physical contacts with mitochondrial outer membranes. Ceramide might thus be directly transferred from the plasma membrane to the mitochondrial outer membrane. It is conceivable that this “kiss-of-death” increases the permeability of the mitochondrial outer membrane thereby triggering apoptosis

New Data on Large Brown Bear (Ursus arctos L., 1758, Ursidae, Carnivora, Mammalia) from the Pleistocene in Yakutia

New finds of brown bear (Ursus arctos L., 1758) fossil remains from the territory of Yakutia, namely, skulls and mandibular bones, have been investigated. The new finds are exceptionally large: most dimensions of these specimens exceed those of the present-day brown bears of Yakutia and even the maximal parameters of the largest individuals of the present-day Eurasian subspecies U. a. beringianus and U. a. piscator. Analysis of various data showed that giant brown bears had inhabited northern Yakutia during the Karginian interstadial in the Late Pleistocene