Abstract
Mitochondria, key organelles of eukaryotic cells that are responsible for essential metabolic processes, generation of energy, cellular redox state and many other processes, are deeply involved in cellular homeostasis and influence overall cell/organism physiology. Defects in mitochondria can lead to a number of different disorders in mammals [1]. Changes in the functional state of mitochondria can induce cellular responses via activation of “mitochondrial retrograde signaling” pathway(s). Such responses often result in changes in gene expression and overall cell physiology leading to the prevention of cell death, as described in mammals and yeast [2]. In mammals, physiological changes induced by retrograde signaling are often linked to cancer-related disorders, including the activation of different oncogenic factors and enzymes involved in aerobic glycolysis [1]. The major pathway involved in retrograde signaling in yeast (the RTG pathway) is mediated by three activators Rtg1p, Rtg2p and Rtg3p. Rtg2p transfers the signal from mitochondria to the Rtg1p/Rtg3p heterodimeric transcriptional activator that translocates from cytosol to nucleus and activates expression of numerous genes involved in yeast metabolic reprogramming. The RTG pathway is negatively regulated by Mks1p and Bmh1p/2p. TORC1 negative regulation has also been observed [3]. The activation of anaplerotic reactions and peroxisomal functions, including the glyoxylate cycle, has long been considered to be a major RTG pathway response in yeast and the CIT2 gene, encoding the peroxisomal isoform of citrate synthase, as a typical target of the RTG pathway.
Highlights
Mitochondria, key organelles of eukaryotic cells that are responsible for essential metabolic processes, generation of energy, cellular redox state and many other processes, are deeply involved in cellular homeostasis and influence overall cell/organism physiology
The “Cit2p-branch” is active in upper L cells and activates CIT2 expression and related metabolic reprogramming that may lead to production of glutamate/glutamine potentially released from these L cells and consumed by neighboring U cells
The fact that U and L cells gain differently altered mitochondria swollen dampened mitochondria in U cells versus respiratory competent mitochondria with increased reactive oxygen species (ROS) in L cells - suggests the intriguing possibility that differential mitochondrial status is involved in the specification of a particular branch of RTG signaling
Summary
Mitochondria, key organelles of eukaryotic cells that are responsible for essential metabolic processes, generation of energy, cellular redox state and many other processes, are deeply involved in cellular homeostasis and influence overall cell/organism physiology. ROS-free mitochondria activate the “Ato-branch” of RTG signaling in modestly respiring U cells, leading to the activation of expression of ATO1 and ATO2 genes, involved in ammonia production and metabolic reprogramming of these cells [4]. Contrary to previous reports, describing negative regulation of RTG signaling by TORC1, the “Ato branch” is active in parallel with active TORC1 in U cells [5, 7].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
