Growth, Differentiation and Sexuality

Fig. 10.3. Copper delivery to the cytochrome c oxidase subunits
COX1 and COX2, based on data from yeast. Copper
in the medium is reduced to Cu + by the ferric reductase
FRE1. The high-affinity copper transporter CTR3 transports
copper into the cell. By unknown mechanisms, copper
is transported into the mitochondria, where COX17 delivers
copper to the COX assembly factors SCO1 and COX11.
The latter transfer the metal to the CuA and CuB site of
cytochrome c oxidase. A recent publication (Cobine et al.
2004) demonstrates a non-proteinaceous copper pool in the
mitochondrial matrix, and suggests a route of copper via the
mitochondrial matrix to the respiratory chain
ent respiratory complexes (I, IV and V, compare
Fig. 10.1). The mutant strain shows severe defects
in complexes I and IV, consistent with an increased
life span and a reduced ROS production. Interestingly,
the severity of the phenotype is dependent
on the allele of the nuclear rmp1 gene, suggesting
an involvement of the RMP1 protein in the OXA1-
Fig. 10.4. A,B The PaCox17 deletion strain ΔPaCox17
(Stumpferl et al. 2004). A Phenotype of ΔPaCox17 in
comparison to wild-type strain s. B Copper supply within
ΔPaCox17. Since PaCtr3 expression is not affected in
ΔPaCox17, the cytosolic copper concentration supports the
Fungal Senescence and Longevity 195
dependent protein assembly (Sellem et al. 2005).
Unfortunately, the function of RMP1 is still unknown.
Overall, the investigation of different long-lived
strains of P. anserina revealed a striking correlation
of life span and respiration type. This correlation
raises the question of whether it is the AOX respiration
per se which is responsible for the longevity
of the corresponding mutant strains. In fact, this
possibility has been disproved, because the overexpression
of AOX in a Cox5:ble background was
reported to lead to an increase in ROS production,
and even restores early senescence in this longlived
strain (Lorin et al. 2001). Evidently, it seems
that there is a delicate tuning of different processes
involved in life span control in P. anserina.Collectively,
the data support the free radical theory of
aging put forward by D. Harman almost 50 years
ago, and since then modified and extended (Harman
1956, 1981, 1998). In particular, the mitochondrial
free radical theory, which proposes that the
generation of mitochondrial ROS is most important
for aging, is supported by the available data
from P. anserina aging. Every process leading to
a decline in ROS production or availability leads to
an increased life span. Processes of this kind are
the lowered generation by an alternative respiration
but also by the ability of remodelling damaged
respiratory chains via protein turnover, a process
depending on the stability of both the mitochondrial
as well the nuclear genome.
formation of active PaSOD1. PaMT1 is induced. However,
lack of PaCOX17 results in mitochondrial copper deficiency,
leading to COX impairment and AOX respiration. In the
mitochondrion, PaSOD2 is present and the mtDNA is
stabilised