Research

Mitochondrial metabolism and cellular senescence in aging research

Current work spans molecular mechanisms, disease relevance, and computational support for aging research.

Research focus

A short orientation before the detailed topics.

Our research group with focus on Mitochondrial Metabolism and Cellular Senescence was founded in mid 2020 as part of the Institute for Biomedical Aging Research, University of Innsbruck, expanding from the research group with focus on Molecular and Cell Biology.

Age-related diseases, including neurodegenerative disorders, cardiovascular disease, diabetes, and cancer, remain a major challenge for society. Aging and cancer are closely linked biological phenomena, and increasing evidence points to metabolic regulation as a central determinant of aging and lifespan.

By searching for new mitochondrial regulators of cellular senescence, FAH domain containing protein 1 (FAHD1) was identified as a protein differentially expressed in mitochondria from young versus senescent human umbilical vein endothelial cells. Follow-up studies showed that depletion of FAHD1 inhibits mitochondrial electron transport and induces cellular senescence in HUVEC. Our current work asks whether FAHD proteins contribute to proliferation in human cancer cells and whether they can become pharmacological targets in selected malignancies.

Research topics

Grouped into major thematic areas for easier scanning.

Mitochondrial health

Mitochondrial function is increasingly recognized as a major determinant of health and disease, especially in diabetes, cardiovascular disease, metabolic syndrome, cancer, and Alzheimer’s disease.

FAH domain containing proteins. FAHD proteins are members of the FAH superfamily of metabolic enzymes. FAHD1 appears to function in mitochondrial oxaloacetate decarboxylation and may regulate TCA cycle flux, mitochondrial function, calcium-related biology, and senescence. See also PMID 30055189 and this study.
Cancer research. FAHD1 is indispensable for survival in several cancer cell types. The group studies its effects on complex II activity, glutaminolysis, and inhibitor development for possible anti-cancer use.

Cellular senescence

The lab investigates mechanisms that shape the onset and development of cellular senescence to better understand aging at the cellular level.

In vitro models. Work focuses on biomarkers, detection strategies, and combinatorial approaches for senescence assessment in cell systems.
Caenorhabditis elegans. This model organism is used to study lifespan regulation, signaling pathways, and senescence-related phenotypes in vivo.

Computer-aided biology

Computational tools are used to extend experimental biology and support modeling, simulation, and analysis.

Molecular dynamics and docking. In silico simulations and docking help model FAHD1-related biology and inhibitor design.
Machine learning. The lab uses and develops algorithmic approaches for data-driven biological applications related to its research focus.
Software. The group develops and maintains QuMuLuS++ and QMCF2.