Evidence that HxkC, an Aspergillus nidulans mitochondrial hexokinase-like protein, is anti-apoptotic

Margaret E. Katz1, Rebecca Buckland1, and Matthias Brock2,

Author address: 

Molecular and Cellular Biology, University of New England, Armidale, NSW 2351 Australia, [email protected] 2Microbiell Biochemistry, Hans-Knoell-Institut, Beutenbergstr. 11a, Jena 07745,

Abstract: 

Binding of hexokinase II to mitochondria inhibits Bax-induced cytochrome c release from mitochondria and apoptosis in mammalian cells (Pastorino et al, 2002). HxkC, which plays a role in the response to nutrient stress, is the first fungal hexokinase shown to be associated with mitochondria (Bernardo et al. 2007). In a strain lacking functional HxkC, cleavage of DNA into oligonucleosomal fragments, a hallmark of mammalian apoptosis, occurs even in the absence of nutrient stress. This suggests that, as in plants, a fungal mitochondrial hexokinase inhibits programmed cell death even though Bax, a member of the Bcl-2 family, is not present. The hxkC delta null mutant shows increased susceptibility to oxidative stress but increased resistance to rapamycin-induced-inhibition of conidiation. Higher levels of intracellular protease activity, which could be the result of autophagy, are detected in the hxkC delta mutant. To determine whether HxkC plays a role in autophagy, we have generated mutants that lack both HxkC and AtgA, Although no loss of hexokinase activity was detected in the hxkCdelta mutant, purification of HxkC has revealed that the protein possesses low levels of ATPase and glucose-phosphorylating activity. Pastorino J.G., Shulga N., Hoek J.B. (2002) Mitochondrial binding of hexokinase II inhibits Bax-induced cytochrome c release and apoptosis. J. Biol. Chem. 277: 7610-7618. Bernardo S.M.H., Gray K.-A., Todd R.B., Cheetham B.F., Katz M.E. (2007) Characterization of regulatory non-catalytic hexokinases in Aspergillus nidulans. Mol. Genet. Genomics 277: 519-532.
2011

abstract No: 

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Full conference title: 

26th Fungal Genetics Conference
    • Fungal Genetics Conference 26th (2005)