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 | rho0 | 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 | rho0 | 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 | |||