The hypoxic transcription factor KlMga2 mediates the response to oxidative stress and influences longevity in the yeast Kluyveromyces lactis

Abstract

A network of connections among hypoxia, respiration, growth and ageing, mediated by a single protein regulating lipid homeostasis, has been established in yeast.

Light-Stress Response Mediated by the Transcription Factor KlMga2 in the Yeast Kluyveromyces lactis

“…We have demonstrated in previous work (Santomartino et al, 2019a) that KlMga2 is involved in the response to oxidative stress and regulates chronological life span. It has been reported that light can induce ROS generation and oxidative stress in S. cerevisiae (Bodvard et al, 2017).…”

“…One of the most relevant pathway regulated by KlMga2 is the biosynthesis of FAs, and we showed here that also this pathway is influenced by light stress. The connection among light stress, membrane composition or functionality, and KlMga2 is highlighted by the fact that phenotypes of the Klmga2 strains, like growth rate, respiration rate, and mitochondrial morphology, are partially or completely suppressed either by darkness or by unsaturated FAs (Micolonghi et al, 2012;Ottaviano et al, 2015;Santomartino et al, 2019a). Finally, our findings open new perspectives on the role of light in the biology of organisms (apparently) deprived of light sensing proteins and on the role of lipids and membranes in the response to light stress.…”

“…Collapsed mitochondria are often associated to ROS accumulation and impaired response to oxidative stress: we previously observed that GDK/Klmga2 strain showed a stronger protection against ROS by over-expressing ROS detoxification enzymes catalase (Cat) and superoxide dismutase (SOD) in the exponential growth phase as compared to wild type strain (Santomartino et al, 2019a). The deletion of KlMGA2 also caused an increased chronological life span (Santomartino et al, 2019a).…”

“…It is activated in hypoxic conditions by proteasome cleavage (Hoppe et al, 2000): the 90 kDa N-terminal soluble fragment moves then into the nucleus where it induces the expression of low-oxygen responsive genes. In K. lactis, studies on KlMGA2 gene, which is the ortholog gene of S. cerevisiae MGA2 and/or SPT23, revealed multiple cellular roles of this regulator, including response to hypoxia, respiration, glucose metabolism, response to ROS, life span, and general cellular fitness (Micolonghi et al, 2012;Ottaviano et al, 2015;Santomartino et al, 2019a). In detail, the genetic targets of KlMga2 in FA biosynthesis are KlACC1 and FAD2 genes and phenotypes generated by KlMGA2 deletion are restored by the addition of unsaturated FAs (UFA).…”

UPC2 gene deletion modifies sterol homeostasis and susceptibility to metabolic inhibitors in Kluyveromyces lactis

“…Moreover, Kl Mga1p does not regulate KlOLE1 expression, but it induces the transcription of the fatty acid desaturase FAD2 gene, not present in S. cerevisiae (Micolonghi et al, 2012; Ottaviano et al, 2015). Recent work of Santomartino et al (2019) demonstrated the involvement of the Kl Mga2p in regulation of K. lactis ROS metabolism and longevity. In this work, we investigated the role of K. lactis UPC2 gene, the orthologue of the ScUPC2/ScECM22 genes from S. cerevisiae .…”