Project description
Mitochondrial stress responses to understand human disease
Ageing is not only an issue related to society and medicine, but also the biological process occurring on the cellular level. Understanding how cells cope with mitochondrial dysfunction is important because mitochondrial decline is strongly linked to age-related diseases and reduced cellular health. Previous research has identified the OMA1-DELE1-HRI mitochondrial integrated stress response (mitoISR), a signalling pathway responsible for the reaction to mitochondrial dysfunction. The ERC-funded mitoSCALES project investigates which molecules initiate the mitochondrial stress response, and how stress information is encoded, integrated and propagated across biological scales to shape cellular adaptation.
Objective
The increase in human life expectancy and associated rise in late-life morbidities will be a key societal
challenge of this century. Cellular homeostasis dwindles over time and the cellular structure tied to aging and
age-related diseases like no other is the mitochondrion. As the sole endosymbiotic organelles of the human
cell, mitochondria must elaborately interface with their environment—inside the cell and beyond—for the
effective detection, communication and resolution of mitochondrial dysfunction. Until recently, a systematic
and in-depth study of mitochondrial stress responses was infeasible in the human system, but our work has
now created an opportunity for their decryption. Combining genome-wide screening, synthetic biology and
biochemistry, we have discovered and begun to molecularly characterize the key signaling pathway engaged
by human cells in the wake of a wide range of mitochondrial perturbations: the OMA1-DELE1-HRI ‘mitoISR’.
At the level of the organelle, mitoSCALES will identify the molecular triggers of this pathway, the biochemical
interplay of its components and how this relates to their other cellular functions. Molecular understanding of
these processes will be paramount for decoding their role in human pathologies. At the cellular level, we will
elucidate the functional remodeling of the cell in the wake of mitochondrial stress and how this shapes cell
fate decisions. We will particularly examine the crosstalk with a secondary mitochondrial stress response we
term ‘mitoHSR’ and how this can be tuned to bolster cell viability. At the highest level of complexity, we will
create new paradigms for studying cell non-autonomous mitochondrial stress signaling and mitohormesis in
the human system via genomics for the first time.
Altogether, mitoSCALES will decipher mitochondrial stress responses at the molecular, cellular and inter-
cellular level to inspire tomorrow’s biomedical solutions for longer, healthier lives across the population.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry
- natural sciences biological sciences synthetic biology
- natural sciences biological sciences cell biology
- medical and health sciences basic medicine pathology
- medical and health sciences basic medicine physiology homeostasis
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-COG
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80539 Planegg
Germany
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