Mdm38 protein depletion causes loss of mitochondrial K+/ H+ exchange activity, osmotic swelling and mitophagy

K Nowikovsky, S Reipert, Rodney James Devenish, R J Schweyen

Research output: Contribution to journalArticleResearchpeer-review

158 Citations (Scopus)

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.Cell Death and Differentiation advance online publication, 1 June 2007; doi:10.1038/sj.cdd.4402167.
Original languageEnglish
Pages (from-to)1647 - 1656
Number of pages10
JournalCell Death and Differentiation
Volume14
Issue number9
Publication statusPublished - 2007

Cite this