Formation of a Snf1-Mec1-Atg1 Module on Mitochondria Governs Energy Deprivation-Induced Autophagy by Regulating Mitochondrial Respiration

Yi, Cong; Tong, Jingjing; Lu, Puzhong; Wang, Yizheng; Zhang, Jinxie; Sun, Cheng; Yuan, Kangning; Xue, Renyu; Zou, Bing; Li, Nianzhong; Xiao, Shu-Hua; Dai, Chong; Huang, Yuwei; Xu, Liling; Li, Lin; Chen, She; Miao, Dengshun; Deng, Haiteng; Li, Hongliang; Yu, Li

doi:10.1016/j.devcel.2017.03.007

Cited by 71 publications

(79 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Indeed, ATM controls mitochondrial response to nuclear DNA damage (Valentin-Vega et al, 2012;Shimura et al, 2017), and contributes to the maintenance of mtDNA copy numbers in fibroblasts under normal conditions (Eaton et al, 2007). Likewise, ATR is recruited at the mitochondrial periphery to control glucose starvation-induced autophagy in yeast (Yi et al, 2017), and was shown to suppress cytochrome c release from mitochondria, thereby inhibiting apoptosis (Hilton et al, 2015). Reciprocally, the sensing of mtDNA damage can trigger the relocalization of repair-related proteins in mitochondria, including p53 (Wong et al, 2009;Boesch et al, 2011), the SOG1 functional homologue.…”

Section: Discussionmentioning

confidence: 99%

Role of pyrimidine salvage pathway in the maintenance of organellar and nuclear genome integrity

et al. 2018

View full text Add to dashboard Cite

Summary Nucleotide biosynthesis proceeds through a de novo pathway and a salvage route. In the salvage route, free bases and/or nucleosides are recycled to generate the corresponding nucleotides. Thymidine kinase (TK) is the first enzyme in the salvage pathway to recycle thymidine nucleosides as it phosphorylates thymidine to yield thymidine monophosphate. The Arabidopsis genome contains two TK genes −TK1a and TK1b− that show similar expression patterns during development. In this work, we studied the respective roles of the two genes during early development and in response to genotoxic agents targeting the organellar or the nuclear genome. We found that the pyrimidine salvage pathway is crucial for chloroplast development and genome replication, as well as for the maintenance of its integrity, and is thus likely to play a crucial role during the transition from heterotrophy to autotrophy after germination. Interestingly, defects in TK activity could be partially compensated by supplementation of the medium with sugar, and this effect resulted from both the availability of a carbon source and the activation of the nucleotide de novo synthesis pathway, providing evidence for a compensation mechanism between two routes of nucleotide biosynthesis that depend on nutrient availability. Finally, we found differential roles of the TK1a and TK1b genes during the plant response to genotoxic stress, suggesting that different pools of nucleotides exist within the cells and are required to respond to different types of DNA damage. Altogether, our results highlight the importance of the pyrimidine salvage pathway, both during plant development and in response to genotoxic stress.

show abstract

Section: Discussionmentioning

confidence: 99%

Role of pyrimidine salvage pathway in the maintenance of organellar and nuclear genome integrity

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Additionally, the subcellular localisation dynamics of SnRK1 itself adds to the complexity of this question. For yeast SNF1, transient complex formation at mitochondria has been described recently . Although it is accepted that the regulatory beta subunits are responsible for AKIN10 partitioning between nucleus and cytoplasm , detailed knowledge on the location of transient signalling complex formation, as has been observed in yeast, is still missing in plants.…”

Section: Discussionmentioning

confidence: 99%

Redox state‐dependent modulation of plant SnRK1 kinase activity differs from AMPK regulation in animals

et al. 2017

View full text Add to dashboard Cite

The evolutionarily highly conserved SNF1‐related protein kinase (SnRK1) protein kinase is a metabolic master regulator in plants, balancing the critical energy consumption between growth‐ and stress response‐related metabolic pathways. While the regulation of the mammalian [AMP‐activated protein kinase (AMPK)] and yeast (SNF1) orthologues of SnRK1 is well‐characterised, the regulation of SnRK1 kinase activity in plants is still an open question. Here we report that the activity and T‐loop phosphorylation of AKIN10, the kinase subunit of the SnRK1 complex, is regulated by the redox status. Although this regulation is dependent on a conserved cysteine residue, the underlying mechanism is different to the redox regulation of animal AMPK and has functional implications for the regulation of the kinase complex in plants under stress conditions.

show abstract

“…The role of autophagy in starvation for glucose-grown cells is controversial. A few studies conclude that autophagy is neither activated nor necessary for short-term survival during starvation (12, 32); whereas, other studies suggest the opposite (8, 33). We observed that autophagy is essential for cell survival after glucose starvation within 7 days and that ATP levels depended on autophagy within the first 24h of starvation.…”

Section: Discussionmentioning

confidence: 99%

Lipid digestion and autophagy are critical energy providers during acute glucose depletion in Saccharomyces cerevisiae

Weber¹,

Sekar

Tang³

et al. 2019

Preprint

View full text Add to dashboard Cite

14The ability to tolerate and thrive in diverse environments is paramount to all living 15 organisms, and many organisms spend a large part of their lifetime in starvation. Upon acute 16 glucose starvation, yeast cells undergo drastic physiological and metabolic changes and 17 reestablish a constant -though lower -level of energy production within minutes. The 18 molecules that are rapidly metabolized to fuel energy production under these conditions are 19 unknown. Here, we combine metabolomics and genetics, to characterize the cells' response 20 to acute glucose depletion and identify pathways that ensure survival during starvation. We 21 show that the ability to respire is essential for maintaining the energy status and to ensure 22 viability during starvation. Measuring the cells' immediate metabolic response, we find that 23 central metabolites drastically deplete and that the intracellular AMP to ATP ratio strongly 24 increases within 20-30 seconds. Furthermore, we detect changes in both amino acid and 25 lipid metabolite levels. Consistent with this, bulk autophagy, a process that frees amino 26 acids, as well as lipid degradation via β-oxidation contribute in parallel to energy 27 maintenance upon acute starvation. In addition, both these pathways ensure long-term 28 survival during starvation. Thus, our results identify bulk autophagy and β-oxidation as 29 important energy providers during acute glucose starvation. 30 31

show abstract

Formation of a Snf1-Mec1-Atg1 Module on Mitochondria Governs Energy Deprivation-Induced Autophagy by Regulating Mitochondrial Respiration

Cited by 71 publications

References 46 publications

Role of pyrimidine salvage pathway in the maintenance of organellar and nuclear genome integrity

Role of pyrimidine salvage pathway in the maintenance of organellar and nuclear genome integrity

Redox state‐dependent modulation of plant SnRK1 kinase activity differs from AMPK regulation in animals

Lipid digestion and autophagy are critical energy providers during acute glucose depletion in Saccharomyces cerevisiae

Contact Info

Product

Resources

About