title: Mdm38 protein depletion causes loss of mitochondrial K+/H+ exchange activity, osmotic swelling and mitophagy.
abstract: Loss of the MDM38 gene product in yeast mitochondria results in a variety of phenotypic effects including reduced content of respiratory chain complexes, altered mitochondrial morphology and loss of mitochondrial K(+)/H(+) exchange activity resulting in osmotic swelling. By use of doxycycline-regulated shut-off of MDM38 gene expression, we show here that loss of K(+)/H(+) exchange activity and mitochondrial swelling are early events, associated with a reduction in membrane potential and fragmentation of the mitochondrial reticulum. Changes in the pattern of mitochondrially encoded proteins are likely to be secondary to the loss of K(+)/H(+) exchange activity. The use of a novel fluorescent biosensor directed to the mitochondrial matrix revealed that the loss of K(+)/H(+) exchange activity was immediately followed by morphological changes of mitochondria and vacuoles, the close association of these organelles and finally uptake of mitochondrial material by vacuoles. Nigericin, a K(+)/H(+) ionophore, fully prevented these effects of Mdm38p depletion. We conclude that osmotic swelling of mitochondria triggers selective mitochondrial autophagy or mitophagy.
authors.affiliation: Department of Genetics, Max F Perutz Laboratories, University of Vienna, Vienna, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Nowikovsky
authors.forename: S
authors.initials: S
authors.lastname: Reipert
authors.forename: R J
authors.initials: RJ
authors.lastname: Devenish
authors.forename: R J
authors.initials: RJ
authors.lastname: Schweyen
mesh_terms: D001343:Autophagy; D015870:Gene Expression; D006859:Hydrogen / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins; D008933:Mitochondrial Swelling; D009154:Mutation; D011188:Potassium / Q000378:metabolism*; D027961:Potassium-Hydrogen Antiporters / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C488529:MDM38 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D027961:Potassium-Hydrogen Antiporters; D029701:Saccharomyces cerevisiae Proteins; D006859:Hydrogen; D011188:Potassium