Scientists Revive Failing Cells With Mitochondria Transplants

Our cells produce energy in biological power plants called mitochondria. These energy-makers have minds of their own. They operate using a unique set of DNA and can travel outside cells. Like astronauts, they often escape in fatty bubbles, land on other cells, explore them, and sometimes literally fuse with native mitochondria in their new homes.

This makes mitochondrial diseases hard to treat. Few gene editing tools can reach them and fix genetic typos. Even without mutations, mitochondria falter with age, contributing to diabetes, Alzheimer’s disease, heart failure, and other medical scourges.

But an experimental fix is gaining traction. Researchers are shuttling healthy mitochondria into cells—essentially transplanting them—to restore energy production and reboot metabolism.

There’s a major roadblock, however. Getting healthy mitochondria to the right cells is challenging. Scientists at the Institute of Molecular and Clinical Ophthalmology Basel have now developed a system that tethers donated mitochondria to their targets.

Called MitoCatch, the scientists engineered matching proteins and attached them to donor mitochondria and recipient cells. Like hook-and-eye fasteners, the binders pull the two partners into close contact. From there—by mechanisms that are still mysterious—the new mitochondria ride in on fatty bubbles, disembark inside the cell, and get to work.

In the study, the researchers delivered mitochondria to multiple cell types, and an injection of mitochondria saved vulnerable retinal cells in mice with inherited blindness.

“As a therapy, mitochondria transplantation has been hindered by the lack of tools to target healthy mitochondria directly to disease-affected cells,” wrote Samantha Krysa and Jonathan Brestoff at Washington University School of Medicine, who were not involved in the study.

MitoCatch overcomes this barrier.

Domesticated Bacteria

Roughly two billion years ago, an ancestral cell ate a bacterium. But rather than digesting it, the cell formed an unlikely alliance with its erstwhile prey. The bacterium converted oxygen into energy for the host, and received protection and nutrients in return. Over time, the bacterium gave up its independence and became a critical part of our cells: mitochondria.

Unlike other cell structures called organelles, mitochondria carry 37 unique genes that encode the core components of their energy-making machinery. Their stripped-down genome leaves little margin for error and is especially vulnerable to mutation. It’s also shielded by a double membrane, making it difficult to reach using conventional biotech tools.

But mitochondria have a superpower: They can leave host cells. Research from the last two decades shows that many cells export some mitochondria into the cellular void. The practice could be a way to rid themselves of damaged mitochondria or to deliver healthy ones to struggling neighbors, like an intercellular care package.

This quirk led to the idea of mitochondrial transplantation. Here, healthy mitochondria are injected into tissue or the bloodstream to treat damaged cells. Early results are encouraging. Transplant extends the healthy lifespan of mice with mitochondrial defects, limits injury after stroke or heart attack, accelerates wound healing in people, and hints at benefits for obesity.

Because nearly every human cell depends on mitochondria for energy—and falters when they break—transplantation could unlock treatments for a broad range of diseases hard to treat today. That is, if healthy replacements can reach their destination.

“Being able to deliver mitochondria efficiently to the right cell types has been a key hurdle for this therapeutic strategy,” wrote Krysa and Brestoff.