Research Themes Mitochondrial diseases

Mitochondrial diseases About theme

The mission of the theme is to understand cellular bioenergetics in health and disease at all levels of complexity.

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Mitochondrial diseases About theme

The mission of the theme is to understand cellular bioenergetics in health and disease at all levels of complexity. The gained knowledge will enable us to develop preventive and supportive measures and substantial contributions towards the development of rational treatment strategies for mitochondrial diseases.
 
Human cells require energy in the form of ATP to function adequately. In most cell types, ATP is primarily generated by mitochondria, which are also key players in other cellular processes, such as adaptive thermogenesis, ion homeostasis, innate immune responses, and programmed cell death (apoptosis). Mitochondrial dysfunction, defined as a disturbance in the function of the oxidative phosphorylation system, is not only observed in monogenic mitochondrial disorders but is also associated with more common pathologic diseases and conditions, such as genetic forms of Parkinson’s disease, certain types of cancer like pheochromocytomas, heart failure, diabetes mellitus, epilepsy, and with adverse drug effects like nucleoside reverse transcriptase inhibitors (NRTIs).

To realize this mission, we defined three lines of research along the spectrum of molecule-man-population: (i) structure and function of molecules and complexes; (ii) cellular consequences of hampered oxidative phosphorylation; (iii) clinical aspects of mitochondrial diseases.
  • Structure and function of molecules and complexes
  • Cellular consequences
  • Clinical aspects

Objectives

  • We aim to identify new gene defects in the oxidative phosphorylation system and to characterize the cellular mechanisms involved.
  • We aim to elucidate the molecular mechanism and regulation of mitochondrial complex I based on the atomic structure.
  • We aim to resolve the complete assembly pathway of mitochondrial complex I and to identify and functionally characterize new components of the assembly machinery.
  • We will study the dynamics of the mitochondrial complexome in health and disease.
  • We will explore the tissue-specific inventory and regulation of the complexes of oxidative phosphorylation and their correlation with specific phenotypes.
  • We will investigate the links and mechanisms connecting genetic defects with organ-specific disease phenotypes.
  • We will further develop tools to monitor the metabolic state and bio-energetic status of mitochondria in living cells and tissues.
  • We will study the influence of environmental factors on the progression of mitochondrial disease.
  • We will develop a toolbox of biomarkers and relevant clinical outcome measures to monitor progression of mitochondrial disease and the effect of therapeutic interventions.
  • We will perform long-term follow-up studies on defined patient cohorts.
  • We will explore new therapeutic approaches to mitochondrial diseases.

Theme leader

Jan Smeitink MD PhD
full professor

+31 (0)24 361 44 30

Contact

News and agenda

Organisation


Researchers Mitochondrial diseases

See the researchers related to this theme.

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Centers of clinical expertise

Information might be only available in Dutch.


The Radboud Center for Mitochondrial Medicine

The RCMM is an international expert center for clinical care, diagnostics and research for patients with or suspected of having a mitochondrial energy disorder. go to center (Dutch)

European Reference Networks

The theme is linked to the European Reference Networks. read more

Answers in Dutch

Information on our research can also be found in Dutch on the Nationale Wetenschapsagenda website. The information here answers questions asked by Dutch citizens. Nationale Wetenschapsagenda

Research group leaders

Affiliated institutes and centers

Donders Institute for Brain, Cognition and Behaviour

The mission of the Donders Center for Medical Neuroscience is to carry out world class research that advances our knowledge on how the nervous system develops and functions and how it is altered by disease, injury, genetic, and environmental factors like stress. read more

Radboud Institute for Health Sciences

Ideally, every procedure in clinical practice and public health should take place based on proof, instead of intuition or 'experience'. Our aim is to improve clinical practice and public health.

Radboud Institute for Molecular Life Sciences

Our main aim is to achieve a greater understanding of the molecular mechanisms of disease. By integrating fundamental and clinical research, we obtain multifaceted knowledge of (patho)physiological processes. read more

Radboudumc Technology Center Clinical studies

Radboudumc provides professional support in the conduct of clinical research involving human subjects.

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Radboudumc Technology Center Mass spectrometry

The Technology Center for Mass Spectrometry offers high-level expertise in bioanalytical mass spectrometry combined with in-depth knowledge on biomedical and clinical applications, embedded in a cutting-edge clinical and fundamental research environment.

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Radboudumc Technology Center Microscopy

The Microscopic Imaging Center offers access to both standard and innovative advanced microscopy infrastructure and applications including technical operator-assistance and in-depth microscopic imaging knowledge.

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Radboudumc Technology Center Bioinformatics

The Bioinformatics technology center aims to raise and solve biological questions using the most recent computer technologies and big data solutions.

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Radboudumc Technology Center Animal research facility

This technology center offers advice and support from planning up to and including the conduct of animal research on behalf of biomedical research and education.

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