Role of HxkC, a mitochondrial hexokinase-like protein, in fungal programmed cell death.

ABSTRACT

Apoptosis is a form of programmed cell death (PCD) that occurs during animal development and is also triggered by a variety of signals including nutrient or oxidative stress, hypoxia, DNA damage, viral infection and oncogenic transformation. Though apoptotic-like PCD also occurs in plants and fungi, genes encoding several of the key players in mammalian apoptosis (p53 and BH-domain proteins) have not been identified in these kingdoms. In this report we investigated whether HxkC, a mitochondrial hexokinase-like protein, and XprG, a putative p53-like transcription factor similar to Ndt80, play a role in programmed cell death in the filamentous fungus Aspergillus nidulans. We show that a mutant lacking HxkC is more sensitive to oxidative stress. Autolysis, a form of fungal programmed cell death triggered by carbon starvation, is accelerated in the hxkCΔ1 mutant but not the hxkCΔ1 xprGΔ1 double mutant. In the absence of nutrient stress, the hxkCΔ1 mutant displays XprG-dependent DNA fragmentation typical of apoptosis and elevated levels of intracellular protease. HxkC and XprG are required for catabolism of N-acetylglucosamine, as in Trichoderma reesei. We show that XprG is present in the nucleus. We conclude that, like mammalian mitochondrial hexokinase, HxkC has anti-apoptotic activity and the XprG transcription factor has a pro-apoptotic role in filamentous fungi.