Mitochondria are able to detect at an early stage whether they are under stress and take appropriate measures to prevent further damage. This has been discovered by a research team from the Universities of Freiburg and Heidelberg. Mitochondria supply cells with energy, which is why they are also known as the ‘powerhouses of the cell’. At the same time, reactive oxygen species (ROS) are produced within them, which play a key role in ageing processes and numerous diseases. “Our findings show that mitochondria can monitor themselves even before the damage spreads to the rest of the cell,” says Prof. Dr Chris Meisinger, Professor of Biochemistry at the University of Freiburg and member of the Cluster of Excellence CIBSS – Centre for Integrative Biological Signalling Studies.

Previously, research assumed that mitochondria only sound the alarm once the damage is so severe that stress signals escape from the mitochondria into the cytosol. However, the research team led by Meisinger and Prof. Dr Nora Vögtle, Professor of Molecular Biology at Heidelberg University and member of the Cluster of Excellence CIBSS – Centre for Integrative Biological Signalling Studies, has now been able to show that mitochondria react much earlier: even low levels of oxidative stress activate a previously unknown early warning system within them. The findings have been published in the prestigious journal Molecular Cell.

Protein aggregates as a warning signal

The study focuses on two enzymes that normally process newly imported proteins in the mitochondria. Under mild oxidative stress, however, these enzymes lose their function. This leads to the formation of protein aggregates inside the mitochondria, which serve as a warning signal and trigger a protective response in the cell – the so-called mitochondrial stress response (UPR^mt).

For their study, the research team developed a new experimental model in yeast cells that generates controlled, low levels of hydrogen peroxide directly within the mitochondria. Unlike previous methods, this system mimics natural ageing and stress processes much more realistically. In addition to researchers from the Universities of Freiburg and Heidelberg, members of the University of Münster and Stockholm University were also involved in the study.

New therapeutic treatments

The new findings make an important contribution to our understanding of age-related diseases and mitochondrial dysfunction. “We assume that similar mechanisms also exist in human cells, so that our findings will, in the long term, open up new avenues for treatments for neurodegenerative diseases or metabolic disorders,” says Vögtle.

Original publication:

Asli Aras Taskin, Sahana Shankar, Carlotta Peselj, Annette Flotho, Maria Gomez-Fabra Gala, Daniel Poveda-Huertes, Lisa Myketin, Duygu Mutlu, Adinayarana Marada, Sebastian Schuck, Mandy Jeske, Sabrina Büttner, Marcin Luzarowski, Chris Meisinger & F.-Nora Vögtle (2026): Uncovering the initial response: Intra-mitochondrial surveillance activates the UPRmt. Molecular Cell 86. DOI: https://doi.org/10.1016/j.molcel.2026.05.002

CIBSS profile of  Prof. Dr. Chris Meisinger

CIBSS profile of Prof. Dr. Nora Vögtle

Original press release University of Freiburg

Further Information

• Prof. Dr Chris Meisinger is a professor of biochemistry at the Faculty of Medicine at the University of Freiburg. Since 2019, he has been the spokesperson for the Freiburg Collaborative Research Centre (SFB1381) ‘Dynamic organization of cellular protein machineries: From biogenesis and modular assembly to function’. Prof. Dr Nora Vögtle is Professor of Molecular Biology at Heidelberg University and serves as a board member of the Collaborative Research Centre 1381
• The study was funded by the German Research Foundation.