Linking Peroxiredoxin and Vacuolar-ATPase Functions in Calorie Restriction-Mediated Life Span Extension

Table 1

Common denominators of v-ATPase and peroxiredoxin functions in yeast which might impinge on calorie-restriction-mediated life span extension. For more details see the text. O/e: overexpression; Fe: iron; Δ: deletion mutant.

	Protein kinase A	H2O2 resistance	Fe-metabolism
Vacuolar ATPase	v-ATPase disassembly [101] and v-ATPase-driven vacuolar acidification [11] both inhibited in strains lacking IRA2	vma2Δ (V1 domain) and vma3Δ (V0) mutants very sensitive to H2O2 at permissive pH 5 [112]	O/e VMA1 or VPH2 suppressed age-induced loss of mitochondrial membrane potential [11]. Age-induced loss of mitochondrial DNA causes loss of membrane potential and defects in Fe/S-cluster biogenesis [113]
	v-ATPase activity regulates PKA activity upon glucose addition [14]	vph1Δ (V0 vacuole) moderately sensitive to H2O2 at pH 5 [112]	v-ATPase inhibition by concanamycin A caused rapid loss of mitochondrial membrane potential [11]
			Reduced v-ATPase function suppresses defects associated with the loss of mitochondrial DNA and membrane potential [114]
			Aft1 is required for the survival of a strain lacking VMA2 [115]
Peroxiredoxins	Tsa1 peroxidase function stimulated at low PKA activity (gpa2Δ, gpr1Δ, cdc35-1, o/e PDE2) [12]	tsa1Δ sensitive to H2O2 but not tert-butyl-OOH [116]	O/e FRA1 suppressed slow growth and increased Aft1-dependent transcription in a strain lacking mitochondrial high-affinity Fe-transport (mrs3Δ mrs4Δ), in a TSA1 dependent manner; Tsa1 interacts physically with Fra1 [117]
			Tsa1 and Tsa1Cys48 are required for aerobic growth of an mrs3Δmrs4Δ strain [117]
	Tsa2 levels increased at low PKA activity (ras2Δ) [88]	tsa2Δ slightly resistant to H2O2 [12], tsa1Δ tsa2 more sensitive than tsa1Δ [70]	Tsa2, as well as Tsa2C48, represses the expression of an Aft1-target (FIT2) in wt and vma2Δ, Tsa2 binds to Fra1 in vma2Δ, increased TSA2 levels in vma2Δ suppressed by Fe supplementation [115]