Mechanisms Underlying the Essential Role of Mitochondrial Membrane Lipids in Yeast Chronological Aging

Table 1

In yeast cells that progress through diauxic (D), postdiauxic (PD), and stationary (ST) growth phases, LCA elicits three different patterns of changes in concentrations of various mitochondrial proteins. These patterns are called “regulon type 1,” “regulon type 2,” and “regulon type 3.” Every type of these regulons includes a partial mitochondrial dysfunction (PMD) regulon and an oxidative stress (OS) regulon, each regulated in response to a different aspect of limited mitochondrial function. The PMD and OS regulons are divided into six or four clusters, respectively, each modulated by a different kind of partial mitochondrial dysfunctionality that triggers a distinct cellular response mediated by a distinct set of transcription factors. These transcription factors include Rtg1/Rtg2/Rtg3, Sfp1, Aft1, Yap1, Msn2/Msn4, Skn7, and Hog1. See text for more details. afo1Δ: a mutation eliminating the mitochondrial ribosomal protein Afo1 of the large subunit; ETC: electron transport chain; kgd1Δ: a mutation eliminating the subunit Kgd1 of the mitochondrial alpha-ketoglutarate dehydrogenase complex; kgd2Δ: a mutation eliminating the subunit Kgd2 of the mitochondrial alpha-ketoglutarate dehydrogenase complex; lpd1Δ: a mutation eliminating the lipoamide dehydrogenase component Lpd1 of the pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes; mdl1Δ: a mutation eliminating the mitochondrial ABC transporter Mdl1; rho⁰: a cluster of genes whose transcription is induced in response to complete loss of mitochondrial DNA; ROS: reactive oxygen species; S1: a cluster of genes whose transcription is activated in response to inhibition of mitochondrial translation; TCA: tricarboxylic acid cycle; yme1Δ: a mutation eliminating the catalytic subunit Yme1 of the mitochondrial i-AAA protease complex.

Pattern of age-related concentration change	Regulon	Cluster	Transcription factor(s)	Mitochondrial functions affected
	Partial mitochondrial dysfunction (PMD) regulon 1	rho^0	Rtg 1/Rtg2/Rtg3, Sfp1, Aft1	TCA cycle, glyoxylate cycle, ETC, amino acid synthesis, heme synthesis and attachment, protein synthesis, protein import, protein folding and proteostasis, glycerol degradation, acetaldehyde metabolism
		S1	Rtg 1/Rtg2/Rtg3, Sfp1, Aft1
		General TCA cycle dysfunction	Rtg 1/Rtg2/Rtg3, Sfp1, Aft1
		kgdlΔ, kgd2Δ or lpd1Δ	Rtg 1/Rtg2/Rtg3, Sfp1, Aft1
		ymelΔ mdllΔ	?
		afolΔ	Sfp1
	Oxidative stress (OS) regulon 1	Yap1 governed	Yap1	TCA cycle, glyoxylate cycle, ETC, amino acid synthesis, protein synthesis, protein import, protein folding and proteostasis, mtDNA replication and maintenance
		Msn2/Msn4 governed	Msn2/Msn4
		Skn7 governed	Skn7
		Hog1 governed	Hog1
	PMD regulon 2	rho^0	Rtg 1/Rtg2/Rtg3, Sfp1, Aft1	Protein import, protein folding, and proteostasis
		S1	Rtg 1/Rtg2/Rtg3, Sfp1, Aft1
		General TCA cycle dysfunction	Rtg 1/Rtg2/Rtg3, Sfp1, Aft1
		kgdlΔ, kgd2Δ or IpdlΔ	Rtg 1/Rtg2/Rtg3, Sfp1, Aft1
		yme1Δ mdl1Δ	?
		afolΔ	Sfp1
	OS regulon 2	Yap1 governed	Yap1	Protein import, protein folding and proteostasis, ROS detoxification, stress response and protection, iron-sulfur clusters synthesis and assembly
		Msn2/Msn4 governed	Msn2/Msn4
		Skn7 governed	Skn7
		Hog1 governed	Hog1
	PMD regulon 3	rho0	Rtg1/Rtg2/Rtg3, Sfp1, Aft1	Mitochondrial division
		S1	Rtg1/Rtg2/Rtg3, Sfp1, Aft1
		General TCA cycle dysfunction	Rtg1/Rtg2/Rtg3, Sfp1, Aft1
		kgd1Δ, kgd2Δ or lpd1Δ	Rtg1/Rtg2/Rtg3, Sfp1, Aft1
		lpd1Δ yme1Δ mdl1Δ	?
		afo1Δ	Sfp1
	OS regulon 3	Yap1 governed	Yap1	Mitochondrial division
		Msn2/Msn4 governed	Msn2/Msn4
		Skn7 governed	Skn7
		Hog1 governed	Hog1