Mitochondria are a bit strange. It’s popular to call them the “powerhouses of the cell,” and that’s true. But they’re also long-ago-domesticated free-living organisms that insist to this day on running their own genetic show, with a private genome and dedicated systems for gene expression. Perhaps understandably, biologists have long pictured the inner mitochondrial compartment (the matrix) as a relatively uniform space where all steps of mitochondrial gene expression—from DNA replication to protein synthesis—happen simultaneously. And yet, given that mitochondria are highly dynamic organelles, constantly fusing, dividing, and moving, experts have long wondered how they manage the spatial organization of this complex process. You can explore these questions, and discover a very interesting new answer, in a recent Science Advances paper that introduces us to the existence of “hubs” that house and control the machinery of mitochondrial protein manufacture.
The authors show that protein synthesis doesn’t just happen everywhere; using advanced imaging, they show that these hubs—where new proteins are being made—are physically separated from the mitochondrial DNA (the sites of transcription) and the RNA processing granules. The hubs are busy, dynamic point sources for new proteins, and their activity influences the distribution of newly synthesized components throughout the mitochondrial network.
And there’s a very interesting twist involving stress. Under severe duress, this highly organized system undergoes dramatic remodeling. Specifically, when the RNA helicase SUV3 is depleted—which leads to the accumulation of troublesome double-stranded RNA (dsRNA)—the cell triggers an intrinsic stress response. This involves the reorganization of ribosomal RNA and mRNA into large structures called mtRNA Stress Bodies (MSBs). The formation of MSBs is tightly linked to stress caused by defective proteins, as it coincides with a near-total shutdown of mitochondrial translation. In fact, the authors show that the cell relies on active translation to sense proteotoxic danger before it locks down its machinery. It’s a remarkable demonstration of how spatial organization of the mitochondrial genetic machinery creates regulatory centers that can temporarily shut down protein synthesis when there’s trouble.
It’s a great story about an elegant system in some of the oldest biological machinery on the planet, and it is worthy of beautiful writing like this, from the end of the abstract:
We propose that the spatial organization of nascent polypeptide synthesis into discrete domains serves to throttle the flow of genetic information to support recovery of mitochondrial quality control.
Throttle! Love it.
In Science Advances, 18 April 2025
From the group of Samantha Lewis at UC Berkeley.
Snippet by Stephen Matheson
Image credit: Figure 5 from Begeman et al. cited above (CC BY-NC).