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

Ref ID: 15803

Author:

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

Author address:

Molecular and Cellular Biology, University of New England, Armidale, NSW 2351 Australia, mkatz@une.edu.au 2Microbiell
Biochemistry, Hans-Knoell-Institut, Beutenbergstr. 11a, Jena 07745,

Full conference title:

26th Fungal Genetics Conference

Date: 15 March 2014

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.

Abstract Number: NULL

Conference Year: 2011

Link to conference website: NULL

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