Elucidating the functions and interactions of mitochondrial porin in Neurospora

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Eukaryotic cells contain membrane-bound compartments in which specialized functions occur. Mitochondria house much of the energy-generating machinery in the cell, using substrates produced outside of the organelle, and transporting products back into the cytoplasm. Mitochondria are bound by two membranes, and small molecules pass through the outer membrane via mitochondrial porin, also known as the voltage-dependent anion-selective channel (VDAC). This protein interacts with numerous proteins in and surrounding the mitochondria; these interactions are proposed to regulate basic metabolism, and in higher organisms, the initiation of apoptosis, or programmed cell death. To understand the function of porin, we are using Neurospora as a model organism; it contains a single porin gene, unlike humans which have three, including one essential form. A strain of Neurospora lacking porin has been generated, and suffers from deficiencies in energy-generating components (cytochromes), grows slowly and is cold-sensitive. Its mitochondria have altered structures and protein composition. The proposed work involves further characterizing these changes, and determining the complex set of factors that require porin for normal function. Genetic systems will be developed to express porin variants with defined sequence changes; the effects of these changes on the cells will enable determination of the different functional parts of porin.