Biomedical Engineering Reference
In-Depth Information
breaks and the release of cytochrome
c
from the mitochondrial inter
membrane space to the cytosol accompanied by ultra structural changes
in the mitochondria. Both mitochondria dependant and mitochondria
independent signalling pathways are effective. Autophagy (type II PCD)
represents a self eating mechanism of damaged cells and organelles, and is
the result of lysosome activity. However, autophagy is also one of the major
degradation and recycling systems within the cells, promoting survival
during nutrient starvation (Hamann et al. 2008).
Cells of all living organisms are programmed to self-destruct under
certain conditions. Apoptosis is the most well known form of programmed
cell death. Apoptosis is essential for proper development in higher
eukaryotes. In fungi, apoptotic-like cell death occurs naturally during
ageing and reproduction, and can be induced by environmental stresses
and exposure to toxic metabolites. The core apoptotic machinery in fungi is
similar to that in mammals, but it is generally assumed that the apoptotic
network is less complex and it is of more ancient origin (Sharon et al. 2009).
Apoptotic-like cell death in yeast was fi rst described in
Saccharomyces
cerevisiae
over 10 years ago, but yeast apoptosis remained controversial,
mainly due to its questionable physiological relevance and a lack of
molecular and genomic data (Frohlich and Madeo 2000, Fabrizio and
Longo 2008). Since then, studies including the identifi cation and analysis
of homologs of apoptotic genes (for example the discovery of an apoptotic
phenotype in a yeast strain carrying the CDC48 mutation reported by Madeo
and colleagues in 1997) confi rmed the existence of apoptotic-like cell death
in fungi. The discovery of several yeast orthologues of crucial apoptotic
regulators provided evidence that yeast and metazoan apoptosis are two
versions of the same cellular program. In particular, the fi nding of a caspase
(Madeo et al. 2002), the apoptotic serine protease HtrA2/Omi (Fahrenkrog
et al. 2004), the transkingdom Bax inhibitor BI-1 (Chae et al. 2003), conserved
proteosomal pathways (Cdc6 destruction) and physiological death scenarios
during ageing in yeast established yeast as a tool for apoptosis research
(Madeo et al. 2004).
Apoptosis is one of several types of energy-dependent PCD processes in
which dying cells undergo controlled decomposition and their components
are recycled. This is differentiated from necrotic cell death, which is energy-
independent and is associated with cell perturbation and infl ammatory
response. Apoptosis can follow two major routes; the extrinsic (or death
receptor) and intrinsic (or mitochondrial) pathways (Elmore 2007).
The extrinsic pathway is initiated by extracellular ligands, such as
Fas or tumor necrosis factor, toxins, or other external signals that bind
and activate death receptors on the cell membrane. The intrinsic pathway
can be activated by cell damage or during specifi c developmental stages.
