Researchers have discovered new insights on the role of mitochondria-endoplasmic reticulum contacts (MERCs) in cellular oxidative stress management, highlighting how these contacts facilitate lipid radical transfer.
The study applied advanced NanoBiT technology to create the MERBiT system, allowing scientists to track the reversible formation of MERCs within living cells. This innovation could significantly advance the field of cell biology by providing new ways to analyze organelle interactions.
According to the findings, when mitochondria experience damage and generate reactive oxygen species (ROS), the formation of MERCs increases. This process is driven by the phosphorylation of the tethering protein RMDN3 (also called PTPIP51), which physically links the ER and mitochondria.
Evidence demonstrates the dual role of RMDN3, where it not only strengthens the connection between ER and mitochondria but also aids the retrograde transport of lipid radicals away from mitochondria. These lipid radicals often lead to oxidative damage if allowed to accumulate, putting the cell at risk of death.
The researchers found significant correlations between enhanced RMDN3-VAPB binding during ROS accumulation and improved cell survival. They said, “We propose the function of MERCs in attenuating cell death caused by mitochondrial lipid radical toxicity under conditions of mitochondrial damage.”
This research underpins the importance of organelle interactions and opens up potential therapeutic avenues for addressing mitochondrial dysfunctions, which are linked to various neurodegenerative diseases.
By leveraging the ability to observe these interactions dynamically, the study provides clues to the cellular mechanisms underlying stress regulation. This could lead to novel strategies for enhancing cell resilience against oxidative stress, particularly through enhanced lipid management.
The study suggests more comprehensive investigations are needed to deepen our grasp of the mechanisms prompting MERC assembly and their potential role across different cell types.