Slm35 links mitochondrial stress response and longevity through TOR signaling pathway

Abstract

In most eukaryotic cells mitochondria are essential organelles involved in a great variety of cellular functions. One of the physiological processes linked to mitochondria is aging, a gradual process of damage accumulation that eventually promotes cell death. Aging depends on a balance between mitochondrial biogenesis, function and degradation. It has been previously shown that Tor1, Sch9 and Ras2 are activated in response to nutrient availability and regulate cell growth and division. A deficiency in any of these genes promotes lifespan extension and cell protection during oxidative and heat shock stress. In this work we report that in Saccharomyces cerevisiae, the uncharacterized mitochondrial protein Slm35 is functionally linked with the TOR signaling pathway. A Δtor1Δslm35 strain shows a severe decrease in lifespan and is unable to contend with oxidative and heat shock stresses. Specifically, this mutant shows decreased catalase activity indicating a misregulation of ROS scavenging mechanisms. In this study we show that Slm35 is also relevant for mitochondrial network dynamics and mitophagy. The results presented here suggest that Slm35 plays an important role connecting mitochondrial function with cytosolic responses and cell adaptation to stress and aging.

Mitochondrial Oxidative Stress Impairs Energy Metabolism and Reduces Stress Resistance and Longevity ofC. elegans

“…Mitochondria supply cellular energy and are key regulators of intrinsic cell death and consequently affect longevity [1, 2]. A link between aging and mitochondrial dysfunction has been well established [2–7].…”

“…Mitochondria supply cellular energy and are key regulators of intrinsic cell death and consequently affect longevity [1, 2]. A link between aging and mitochondrial dysfunction has been well established [2–7]. The “free radical theory” of aging, first proposed by Harman et al, explains aging as a result of the accumulation of cellular damage caused by reactive oxygen species (ROS) [2, 8, 9].…”

“…A link between aging and mitochondrial dysfunction has been well established [2–7]. The “free radical theory” of aging, first proposed by Harman et al, explains aging as a result of the accumulation of cellular damage caused by reactive oxygen species (ROS) [2, 8, 9]. Since mitochondria are the primary source of ROS, Harman himself extended his theory to the “mitochondrial theory of aging” [3, 10].…”

Deletion of Autophagy geneATG1and F-box motif encoding geneYDR131Ctogether leads to Synthetic Growth Defects and Flocculation behaviour inSaccharomyces cerevisiae

“…The high throughput studies have reported many genes showing genetic interactions with ATG1 (https://www.yeastgenome.org/locus/S000003148/interaction) involved in various biological processes. The genetic interaction of ATG1 with mitochondrial protein encoding gene AIM25 (A guilar -L opez et al 2016) involved in maintaining the integrity of mitochondrial network and histone deacetylase, HDA1 (R obert et al 2011) and RPD3 showed synthetic growth defects. The Rpd3 histone deacetylase regulates the transcriptional silencing and autophagy by regulating the chromatin remodelling activity (R obert et al 2011).…”

The Small Yeast GTPase Rho5 and Its Dimeric GEF Dck1/Lmo1 Respond to Glucose Starvation

“…Of those, the SNF1 complex participates in the regulation of cell wall composition, suggested by the sensitivity of null mutants towards cell wall stress agents both in S. cerevisiae and in the milk yeast Kluyveromyces lactis [ 13 , 14 ]. In addition, Ras2/cAMP-signaling was also found to affect CWI signaling through genetic interactions and in transcriptome studies [ 15 , 16 ], as well as influencing the dynamics of the actin cytoskeleton [ 17 , 18 ], mitochondrial morphogenesis [ 19 ], pH homeostasis [ 20 ], and apoptosis [ 21 ]. Ras/cAMP signaling has also been connected to nutrient signaling by TORC1 through its downstream kinase Sch9 (reviewed in a previous paper [ 22 ]; see Figure 1 A for an overview of different signaling pathways highlighting the small GTPases involved).…”