88 6 ART for Antiaging
6.2.2.6 Expression Fluctuations of Oxidative Phosphorylation
and Antioxidation Responsible Genes: Dual-Phase Responses
During CR and Mimetic Exposure
The metabolic flux of glucose flows from the cytosol to mitochondria. Because
the cytosolic glycolysis pathway genes are globally downregulated by CR and
mimetics, it could be predicted that the mitochondrial oxidative phosphorylation
pathway genes should be accordingly downregulated by each treatment. Indeed,
it was found that those genes encoding COX (complex IV), F 1 F 0 -ATP synthase
(Complex V), and other associated signature proteins are downregulated in every
group, although the expression levels of those genes are much lower in the CR
group than in the mimetic groups.
The analytic data of transcriptomic microarray indicated that H 2 O 2 degrada-
tion-responsible antioxidant genes, such as Cat1 encoding mitochondria-localized
CAT and Gpx2 encoding cytosolic GSH-POX, are upregulated by CR and mimet-
ics. In contrary, H 2 O 2 generation-responsible antioxidant genes, such as Sod1 and
Sod2 coding for cytosolic copper-zinc SOD (Cu/Zn-SOD) and mitochondrial man-
ganese SOD (Mn-SOD), are downregulated by CR and mimetics, implying that
the main type of ROS in this stage is H 2 O 2 other than O 2 −. Besides, it was also
seen that other antioxidant enzyme-encoding genes are either upregulated (Trx3),
or downregulated (Gto3 and Dot5), or unchanged in different treatment groups.
Table 6.2 ABC transporter
gene expression profiles
in yeast treated by CR and
mimetics
ART artemisinin; CR calorie restrictionABC transporter gene CR H 2 O 2 ART
Plasma membrane
Pdr5 −4.57 −2.33 −1.29
Snq2 1.65 −1.08 1.17
Pdr12 −3.19 2.49 2.96
Pdr15 −3.16 −2.42 −1.44
Aus1 1.31 1.42 1.05
Pdr11 2.43 2.41 2.02
Yor1 −1.12 −1.36 1.02
Ste6 −2.08 −2.12 −2.82
Vacuole membrane
Bpt1 2.23 1.56 1.36
Ybt1 1.06 1.34 −1.11
Ycf1 1.26 1.63 1.54
Mitochondrial membrane
Atm1 2.2 1.15 1.14
Mdl1 −1.37 1.36 1.26
Mdl2 1.18 1.46 1.28
Peroxisome membrane
Pxa1 5.47 −1.66 −1.43
Pxa2 4.11 2.00 1.98