The c subunit is an inner mitochondrial membrane (IMM) protein encoded by three nuclear genes. Best known as an integral part of the F0 complex of the ATP synthase, the c subunit is also present in other cytoplasmic compartments in ceroid lipofuscinoses. Under physiological conditions, this 75 residue-long peptide folds into an α-helical hairpin and forms oligomers spanning the lipid bilayer. In addition to its physiological role, the c subunit has been proposed as a key participant in stress-induced IMM permeabilization by the mechanism of calcium-induced permeability transition. However, the molecular mechanism of the c subunit participation in IMM permeabilization is not completely understood. Here we used fluorescence spectroscopy, atomic force microscopy and black lipid membrane methods to gain insights into the structural and functional properties of unmodified c subunit protein that might make it relevant to mitochondrial toxicity. We discovered that c subunit is an amyloidogenic peptide that can spontaneously fold into β-sheets and self-assemble into fibrils and oligomers in a Ca2+-dependent manner. C subunit oligomers exhibited ion channel activity in lipid membranes. We propose that the toxic effects of c subunit might be linked to its amyloidogenic properties and are driven by mechanisms similar to those of neurodegenerative polypeptides such as Aβ and α-synuclein.

Electrostatic interactions that drive assembly of lipid–gemini surfactant films with DNA in a gene delivery system are revealed by KPFM.

Aquaculture in North America is currently dominated by Atlantic salmon, but there has been an increasing interest in the production of species native to the Pacific coast.Chinook salmon is relatively new to production; therefore, the selection of appropriate stocks is critical. Often genes from wild populations are incorporated into farmed stocks to avoid performance decreases associated with inbreeding. The present study focuses on assessing the immunological performance of one inbred stock and seven outbred/hybrid crosses after challenge with the marine pathogen, Vibrio anguillarum.Throughout exposure challenge to both pathogen and sterile PBS, significant differences in mortality were observed between crosses. Fish were also assessed for major histocompatibility complex (MHC) class II β1 genotype, and although particular alleles did not confer resistance, crosses with better survival had more individuals presenting a heterozygous genotype. The stress induced during infection resulted in several individuals presenting signs of Bacterial Kidney Disease (Renibacterium salmoninarum) indicating that chronic co-infection may have contributed to susceptibility. When spleen samples from the highest and lowest performing hybrid crosses were assessed for cytokine and respiratory burst gene expression throughout bacterial challenge, high surviving crosses presented lower expression of inflammatory cytokine transcripts (IL-1β, IL-6 and TNFα) when compared to low performing crosses. Interestingly, microsatellite analysis revealed no significant differences in inbreeding coefficient or allelic richness between crosses despite observed variation in immune performance.Understanding the impact of outbreeding on the immune function of farmed, and often inbred, Chinook salmon could aid in future development of high-quality aquaculture stocks for this species.

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