Scientists at Heinrich-Heine University Düsseldorf have discovered a cellular pathway that cells use to repair mitochondria through the specific removal of damaged mitochondrial DNA (mtDNA). This process reduces damage within a cell, allowing the cell to maintain its health and function through a recycling process involving a protein complex called a retromer (How Cells Repair Their Power Plants, 2025). Retromers are cellular structures that help mediate intercellular transport of loads such as damaged mitochondrial DNA.

 

This research contrasts with the classical idea of mitophagy—the process by which the cell clears and recycles mitochondria—because it shows how the mechanism degrades specific mtDNA, rather than the entire organelle. According to conventional thought, damaged mitochondria would be signaled through a process called mitophagy. The damaged mitochondria are detected by certain proteins and then labeled with chemical signals. Then, autophagy receptors that attach to the outer membrane of the mitochondria, connecting the mitochondria and the autophagy (Rubio-Tomás, et al., 2023). This connection allows for the formation of the vesicle autophagosome, a double-membraned sac of fluid, which brings the damaged mitochondrion (singular of mitochondria) to the lysosome—an organelle in cells containing degradative enzymes—to be broken down (Rubio-Tomás, et al., 2023). This process would destroy entire mitochondria. 

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However, emerging research suggests that specific mechanisms exist to degrade specific parts of the mitochondria using retromer pathways (How Cells Repair Their Power Plants, 2025). The mechanism prevents damage from accumulating in the mitochondria, and since mitochondria are largely responsible for generating energy in the cell, the maintenance of this organelle is an extremely important process that keeps us healthy. This new research on mitochondrial repair is significant because it could potentially lead to advancements for treating neurodegenerative diseases such as Alzheimer’s. 

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This newly discovered process of mitochondrial recycling heavily relies on the retromer complex, specifically the protein VPS35 (How Cells Repair Their Power Plants, 2025). Vacuolar protein sorting ortholog 35 (VPS35) is a protein that is part of the retromer complex, a structure that transports “cargo” between vesicular structures (Seaman, 2012; Ali & Dholaniya, 2022). In this case, the cargo would include the damaged mtDNA. The role of VPS35 would be to sort the damaged mtDNA so that it could be recycled. As a result, an increased amount of VPS35 could be expected to increase the recycling of damaged mtDNA. Dr. Parisa Kakanj from the University of Cologne confirmed this by finding that the elimination of damaged mtDNA and general mitochondrial function improve “significantly” when the activity of the retromer complex, specifically the protein VPS35, is increased (How Cells Repair Their Power Plants, 2025). Scientists have also found that mutations in the VPS35 protein may relate to neurodegenerative disorders such as Parkinson's Disease, reinforcing the significance of this protein in cellular function (Rowlands & Moore, 2024). This research brings up new possibilities to treat age related conditions and even diseases related to mitochondrial issues. 

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Previously, scientists had believed that mitochondrial recycling was limited to inefficient mechanisms such as mitophagy. Our understanding of mitochondrial mechanisms has improved, however, along with new insights into neurodegenerative diseases which will have lasting impacts on how doctors treat these conditions.

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References 

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Ali, Z., & Dholaniya, P. (2022). Oxidative phosphorylation mediated pathogenesis of Parkinson’s disease and its implication via Akt signaling. Neurochemistry International, 157, 105344–105344. https://doi.org/10.1016/j.neuint.2022.105344 

Heinrich-Heine University Düsseldorf. (2025, April 4). How cells repair their power plants. ScienceDaily. Retrieved April 22, 2025 from www.sciencedaily.com/releases/2025/04/250404140532.htm 

Khot, M., Sood, A., Tryphena, K. P., Khan, S., Srivastava, S., Singh, S. B., & Khatri, D. K. (2022). NLRP3 inflammasomes: A potential target to improve mitochondrial biogenesis in Parkinson’s disease. European Journal of Pharmacology, 934, 175300. https://doi.org/10.1016/j.ejphar.2022.175300 

Rowlands, J., & Moore, D. (2024). VPS35 and retromer dysfunction in Parkinson’s disease. Philosophical Transactions - Royal Society. Biological Sciences, 379(1899). https://doi.org/10.1098/rstb.2022.0384 

Rubio-Tomás, T., Sotiriou, A., & Tavernarakis, N. (2022). The interplay between selective types of (macro)autophagy: Mitophagy and xenophagy. International Review of Cell and Molecular Biology, 129–157. https://doi.org/10.1016/bs.ircmb.2022.10.003 

Seaman M. N. (2012). The retromer complex - endosomal protein recycling and beyond. Journal of cell science, 125 (Pt 20), 4693–4702. https://doi.org/10.1242/jcs.103440