Automated injection and mitochondrial transfer system

• Subject Area: Basic Research in Biology and Medicine
• Term: Funded in 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 559056116

Mitochondria, often referred to as the powerhouses of the cell, are essential organelles in human cells. They possess their own genome, the mitochondrial DNA (mtDNA), which encodes 13 proteins. These proteins are crucial components of the respiratory chain, through which mitochondria generate most of the cell's energy. Mutations in mtDNA and the resulting dysfunctional proteins can significantly disrupt the energy balance of human cells. Neurodegenerative and cardiovascular diseases, in particular, are closely linked to mutations in the mitochondrial genome. Consequently, most mitochondrial diseases have an extremely poor prognosis, as there are currently no curative options. A unique feature of mtDNA is that it is present in numerous (up to 2,000) copies per cell, packaged in distinct units called nucleoids. Not all mtDNA copies are identical: there are subpopulations of nucleoids that may carry one or more mutations in their mtDNA. This phenomenon of genetic diversity of mitochondria within a cell is also known as heteroplasmy. As long as the proportion of mutated mtDNAs is low, the original mtDNA can maintain the undisturbed function of the mitochondria. Only when a threshold is exceeded (often more than 60% mutated mtDNA within a cell), do mitochondrial dysfunctions occur, which then manifest as mitochondrial diseases. The molecular mechanisms that determine the degree of heteroplasmy in somatic cells are largely unexplored and the functional relevance of the different nucleoid populations is unclear. One reason for the lack of understanding of these fundamental molecular mechanisms is the lack of well controllable experimental approaches to manipulate mitochondria in living cultured human cells. With the proposed automated injection and mitochondrial transfer system, it is possible to transfer mitochondria directly between cells with high precision. For example, mitochondria with an altered genome can be transferred into a healthy cell, or healthy mitochondria can be transferred into a genetically altered cell. Both standardized cell culture models and patient-derived cell lines can be used. We expect that this device will provide fundamentally new insights into the molecular mechanisms underlying heteroplasmy, which will open up new pharmacological intervention options and new therapeutic approaches in the future.

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: Automatisiertes Injektions- und Mitochondrientransfersystem
• Instrumentation Group: 5091 Rasterkraft-Mikroskope
• Applicant Institution: Georg-August-Universität Göttingen
• Leader: Professor Dr. Stefan Jakobs