mTOR under stress

Alexander Martin Heberle

    Research output: ThesisThesis fully internal (DIV)

    594 Downloads (Pure)


    The mechanistic/ mammalian target of rapamycin complex 1 (mTORC1) is a metabolic master regulator which integrates amino acid, growth factor, and energy signals to control cellular metabolism. mTORC1 kinase enhances virtually all anabolic processes and inhibits catabolism to promote cell growth. Under stress, mTORC1 also promotes cell survival. Therefore, mTORC1 activity is needed both under favorable and unfavorable conditions to enable growth and survival, respectively. However, mTORC1 hyperactivity leads to cell death due to uncoupling of metabolism and growth from regulatory inputs. Hence, mTORC1 activity has to be finely tuned to (i) promote anabolic processes and cell growth when nutrients are sufficient, and (ii) balance anabolic and catabolic processes and allow cell survival under stress. While the molecular mechanisms mediating anabolic inputs to mTORC1 have been reported in much detail, mechanistic studies on stress-signaling to mTORC1 and mTORC1-mediated adaptation of cellular metabolism are comparably scarce. This thesis centers on the mechanisms which balance mTORC1 activity and function under stress. We identified novel mechanisms that balance anabolic and catabolic processes to sustain survival under stress. Our findings suggest a novel Achilles heel, which can be targeted in cancer.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    • Thedieck, Kathrin, Supervisor
    • Grellscheid, Sushma-Nagaraja, Co-supervisor, External person
    Award date20-Feb-2019
    Place of Publication[Groningen]
    Print ISBNs9789463235013
    Electronic ISBNs9789463235020
    Publication statusPublished - 2019


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