Genetics of Apoptosis

(Barry) #1

genes coding for superoxide dismutase (Barker et al., 1999) or catalase, changes in
atmospheric oxygen partial pressure, and addition of the physiologic antioxidant
glutathione all have the expected distinct effects on life span and indicate a role for
oxygen in the yeast’s aging process (Nestelbacher et al., 2000). Recently, Laun et al.
(2001) found that mitochondria are the source of ROS in senescent yeast cells.
Mitochondria producing ROS are found in senescent cells, but not in virgin cells.
This might suggest another physiologic role of apoptosis in yeast. It should be noted,
however, that the portion of old cells in a yeast culture is extremely low. Suicide of
old cells will not save much energy, but may prevent formation of genetically damaged
daughters of very old mother cells. Currently, it is controversial whether human
senescent cells die apoptotically or necrotically. The present results in yeast apoptosis
favor an apoptotic age-related cell death. Consistently, primary human cells in culture
undergo apoptosis, producing ROS when they become senescent (Jansen-Dürr,
personal communication). The observation of radical-induced apoptosis in senescent
yeast further strengthens the oxygen theory of aging and confirms the similarity of
yeast and higher cell aging finally leading to apoptosis (for a review, see Fröhlich and
Madeo, 2001).


8.

Applications of yeast apoptosis to plant research

Higher plants also exhibit characteristic apoptotic features, such as DNA strand breaks
and exposure of phosphatidylserine (O’Brien et al., 1997), and can be protected from
cell death by expression of the antiapoptotic genes, bcl-xL or CED-9 (Mitsuhara et
al., 1999).
Osmotin, a protein involved in the plant’s defense response, induces apoptosis in
yeast (Narasimhan et al., 2001). Induction of apoptosis is correlated with intracellular
accumulation of ROS and can be linked to the RAS2/cAMP pathway. This is in
accordance with the observation that hyperactivation of the RAS pathway in yeast
results in cell death (Fedor-Chaiken et al., 1990), as RAS signaling is induced by lack
of nutrients.
An Arabidopsis cDNA library has been screened for functional suppressors of Bax-
induced cell death in yeast cells. Pan et al. (2001) found proteins involved in the
detoxification of oxygen radicals and identified the A.thaliana ethylene-responsive
element-binding protein (AtEBP) as a dominant suppressor of Bax-induced cell death
in yeast. Apoptotic phenotypes of bax expression in yeast could be abrogated by
coexpression of AtEBP.
In a similar approach, Moon et al. (2002) identified soybean ascorbate peroxidase
as a suppressor of Bax-induced cell death in yeast. Expression of the peroxidase
prevents oxygen radical generation.
∆1-pyrroline-5-carboxylate (P5C), an intermediate in biosynthesis and
degradation of proline, is assumed to play a role in cell death in plants and animals.
External supply of proline or P5C is toxic to Arabidopsis, suggesting a crucial role of
P5C dehydrogenase in the process of preventing cell death by degrading P5C.


148 GENETICS OF APOPTOSIS

Free download pdf