Diacylglycerol kinase alleviates autophagic degradation of the endoplasmic reticulum in SPT10‐deficient yeast to enhance triterpene biosynthesis

Abstract

A recent study showed that deletion of the gene encoding the transcription regulator SuPpressor of Ty10 (SPT10) increases total phospholipids, and our previous study established a critical link between phospholipids and the mevalonate/ergosterol (MEV/ERG) pathway, which synthesises triterpenes. This study aims to use spt10Δ yeast to improve triterpene production. Though MEV/ERG pathway was highly expressed in spt10Δ yeast, results showed insufficient accumulation of key metabolites and also revealed massive endoplasmic reticulum (ER) degradation. We found a stable, massive ER structure when we overexpressed diacylglycerol kinase1 (DGK1 OE ) in spt10Δ yeast. Analyses of ER-stress and autophagy suggest that DGK1 OE in the spt10Δ strain decreased autophagy, resulting in increased MEV/ERG pathway activity. Heterologous expression of β-amyrin synthase showed significant production of the triterpene β-amyrin in DGK1 OE spt10Δ yeast. Overall, our study provides a strategic approach to improve triterpene production by increasing ER biogenesis while limiting ER degradation.

Heat stress upregulates arachidonic acid to trigger autophagy in sertoli cells via dysfunctional mitochondrial respiratory chain function

“…Moreover, ETC deficiency inhibits autophagy lysosomal hydrolysis either by activating AMPK signaling or by directly activating the lysosomal Ca 2+ channel [ 18 ]. Although previous studies have demonstrated that mitochondria activate the autophagic pathways to alleviate OS in human cells and yeast via Diacylglycerol kinase and All-trans-retinal [ 19 , 20 ], it is unclear which metabolite regulates mitochondrial autophagy under HS in SCs.…”

Heat stress releases arachidonic acid to induce autophagy in Sertoli cells by enhancing ROS-mitochondrial-endoplasmic reticulum stress axis

“…However, dysfunctional mitochondria were associated with decreased ATP synthesis, Ca 2+ imbalance, increased ROS accumulation and lead to oxidative stress (OS) (Ullah et al, 2021). Although mitochondria and ER activate the autophagic pathways to alleviate OS in human cells and yeast via Diacylglycerol kinase and Alltrans-retinal (Ranganathan et al, 2022;Zhang et al, 2020), it is unclear which metabolite regulates mitochondrial and ER induced autophagy under HS in SCs.…”