Biomedical Engineering Reference
In-Depth Information
overproducing YCA1 were not active against synthetic caspase substrates.
They did however cleave P1-Arg and P1-Lys substrates in the same way
as plant metacaspases (Watanabe and Lam 2005). Consequently, YCA1
participation cannot be determined by using synthetic caspase substrates
or inhibitors. The involvement of metacaspases activity in yeast cell death is
questionable as YCA1-independent cell death (Buttner et al. 2007, Váchová
and Palková, 2007) YCA1-independent caspase like activities have been
reported (Váchová and Palková, 2005).
The genome of the pathogenic filamentous fungus
Aspergillus
fumigatus
comprises two types I metacaspases, CasA and CasB. Using
double knockout mutants, neither of these metacaspases were found
to be essential for virulence. Despite the retraction of apoptosis-related
membrane phosphaltidylserine exposure in CasA and CasB double
knockout stationary-phase cultures, stress induced cell death was not
dependent on metacaspases. It was determined that both CasA and CasB
were necessary for growth in the presence of agents inducing endoplasmic
reticulum stress. This advocates a pro survival role for metacaspases rather
than an involvement in cell death processes (Richie et al. 2007).
The role of metacaspases in fungal cell death still remains elusive and
studies have yielded contradictory data. Alternative routes to determining
the exact function of metacaspases could include the identifi cation of their
substrates via direct characterisation of
in vivo
protein processing on a
proteome-wide scale. Also, the determination of the degradome specifi city
of metacaspases may assist in clarifying their role in cell death processes
(Vercammen et al. 2007).
Biotechnological Roles of Metacaspases
To take full advantage of the application of fungal metacaspase genes in
biotechnological roles, it makes sense to consider their natural function
in biological systems. As mentioned previously, it is well documented
that the yeast metacaspase Yca1p has been implicated in an apoptotic-
like cell death programme that is triggered by exposure to a wide variety
of adverse environmental stimuli (Madeo et al. 2002, Bettiga et al. 2004,
Herker et al. 2004, Wadskog et al. 2004, Flower et al. 2005, Khan et al. 2005,
Mazzoni et al. 2005, Reiter et al. 2005, Silva et al. 2005, Weinberger et al.
2005). There is evidence that fungal metacaspases may function to improve
the genetic pool in a community of yeast by eliminating the weaker
members (Fabrizio et al. 2004, Herker et al. 2004). PCD may provide a
similar benefi t to fi lamentous fungi. The mycelium of
A. fumigatus
is
comprised of a community of interconnected hyphal compartments. By
elimination of certain hyphae by means of PCD, the organism may benefi t
