‘Turbocharged’ Mitochondria Power Birds’ Epic Migratory Journeys

These pioneering studies on mitochondrial performance and bird migration highlight the fact that a seasonal response to changing light levels, not physical preparation, triggers crucial subcellular changes, said Wendy Hood, who studies physiological ecology at Auburn University in Alabama; Mesquita worked with her and other colleagues on these questions during his graduate studies.

Humans “have to train for a while before we start to see any changes in the performance of our mitochondria,” she said. With migratory birds, “it’s spring, they get the right light cycles, and their body starts producing more and better, or higher-quality, mitochondria.”

The recent work advances the idea that there are significant ways in which an organism can change, without modifying its underlying genetic makeup, in response to its environment, said Scott McWilliams, a professor of wildlife ecology and physiology at the University of Rhode Island who was not involved in either study. This “phenotypic flexibility” in birds has been shown to vary according to seasons and population, and these studies are some of the first to demonstrate this across species and subspecies at the mitochondrial level.

“Such a theme,” he said, “is centrally important for understanding how birds during migration accomplish their athletic feats.”

Not Your Textbook Mitochondria

Often known as the powerhouses of the cell, mitochondria are organelles that take in oxygen and molecules from food, such as glucose and fatty acids, to generate adenosine triphosphate, or ATP, which is the fuel for most metabolic processes. High school biology students learn this. But recent research has revealed that mitochondria are more complex and dynamic than anyone realized.

“There’s an assumption that all mitochondria are more or less the same,” said Christopher Guglielmo, the director of the Center for Animals on the Move at Western University in Ontario. “And that view, especially in the past decade or so, has changed.”

New tools that let scientists study mitochondrial activity have uncovered surprising diversity. Some mitochondria produce more ATP than others, or produce it more efficiently. The organelles can fuse or break apart, which changes their shape and performance. In some cases, mitochondria can even migrate between cells or specialize for different functions.

These discoveries about mitochondria have led to a new understanding of the evolution of some animal behaviors. “It’s really only been in the last decade or so that you’re seeing more and more studies looking at mitochondria from an ecological and evolutionary perspective,” Hood said. “Mitochondria are certainly an important target of evolutionary processes.”

For example, Guglielmo’s colleague Jim Staples, who studies animal metabolism at Western University, has shown that hibernating ground squirrels lower their metabolism by dramatically decreasing the performance of mitochondria, which allows them to use less molecular energy and therefore survive winter without eating for long stretches of time. Guglielmo, an expert in bird migration, took inspiration from his co-worker to explore whether changes to mitochondria might explain migratory birds’ long-flight superpowers as well.

Coulson, who was a graduate student with Staples and Guglielmo at the time, led a study on the yellow-rumped warbler, a songbird that migrates between Canada, where it nests, and its wintering grounds in the United States, Mexico and the Caribbean. First, during the birds’ fall migration, they captured the southbound songbirds and brought them into the lab. There, they managed the birds’ exposure to light and darkness to create two laboratory groups of “migratory” and “nonmigratory” warblers. Then they looked for differences in the birds’ mitochondria.

The researchers removed the birds’ flight muscles (which required euthanizing them) and separated out the mitochondria. Then they did lab tests to measure the organelles’ oxygen consumption, which serves as a proxy for how much ATP mitochondria can produce to contract those muscles.

“We hypothesize that when birds are migrating, they have a really high demand on their flight muscle in terms of providing energy for muscle contractions,” Coulson said. “Some of these birds can be flying for up to several hours overnight at a really high exercise intensity.”

The scientists found that birds experiencing the “migration” condition had more mitochondria, and that those mitochondria had a greater capacity to make energy, compared to those in the “nonmigratory” birds. This suggested that during migration, the birds’ mitochondria are “turbocharged,” Coulson said. Then, after the journey is done, the mitochondrial landscape reverts to its usual state. The researchers published their findings in the Journal of Experimental Biology in 2024.

“All those turbocharged mitochondria become regular-charged mitochondria, [and] they get rid of the excess ones,” Coulson said. “That way, they can stop potentially wasting energy on traits that they no longer need for that time of the year.”

The Mighty MitoMobile

Emma Rhodes, a graduate student in Hood’s lab at Auburn, has loved birds since she was a child, when she received bird feeders and her first pair of binoculars as gifts. Later, that interest in watching birds evolved into an interest in studying them when she had the opportunity to hold and release a yellow-rumped warbler — her “spark bird,” she said — at a bird-banding station in coastal Alabama. “To see it intimately, like in your hand, and then fly off — it was like, ‘OK, this is what I want to do,’” Rhodes said.

Rather than simulate migratory conditions in a lab, as the researchers in Canada had done, Rhodes and her colleagues decided to collect migratory birds in the wild to ask a similar question: Is the performance of the mitochondria different in birds that are migratory, compared to those that are not?

To find birds to study, Rhodes and Mesquita, a collaborator, needed to migrate, too, with their lab equipment. They drove a mid-size RV painted navy and orange from Alabama to California and back — twice. Inside: a couch, a refrigerated centrifuge, lab benches and other scientific equipment needed to analyze mitochondria. The roving “MitoMobile” lab, despite encountering generator trouble, let the scientists collect white-crowned sparrows at different locations and examine their mitochondria on the spot.

Rhodes and colleagues took advantage of a known difference between subspecies of white-crowned sparrows: Some migrate and others don’t. Gambel’s white-crowned sparrows fly seasonally between California and Alaska, while Nuttal’s white-crowned sparrows live on the California coast year-round. The researchers caught migrating Gambel’s sparrows near Yosemite National Park, where the birds are known to rest during migration, and nonmigratory Nuttal’s sparrows north of San Francisco in the Marin Headlands.

Independently from the group in Canada, Rhodes and her colleagues found that the flight muscles of migratory white-crowned sparrows had more numerous and more efficient mitochondria, which used more oxygen, compared to the birds that didn’t migrate. While mitochondrial oxygen consumption was highest during migration, researchers observed that it ramped up before the birds began migrating.

Using data from the same birds, Mesquita explored what mechanisms could be responsible for the mitochondria’s increased performance. He focused his search on protein markers that are associated with mitochondrial remodeling — where the organelles change shape by fusing or breaking off.

Mesquita and colleagues found protein markers of dynamic mitochondrial changes in the migratory birds’ pectoral muscles, which are crucial to flight, with fewer in their leg muscles or in any muscles of the nonmigrants. These markers are correlated with how well mitochondria consume oxygen and therefore produce energy.

The theory goes that some mitochondria fuse to improve the production of ATP, while others break apart to get rid of dysfunctional parts. “We don’t know if that’s exactly what’s going on,” Hood said, “but there’s clearly some changes in morphology that are occurring.”

The findings suggest that changes in mitochondrial shape could play a direct role in giving birds their energy boost for long flights — a cellular adaptation that helps explain how such small birds can migrate such vast distances.

Turbocharged mitochondria come with a downside, however. In the process of providing energy, mitochondria produce damaging molecules, known as reactive oxygen species, that can lead to health effects such as cardiovascular disease. If migratory birds build up more numerous and more powerful mitochondria, how do they deal with this tradeoff?

Diet may be one answer. Research by McWilliams and colleagues has shown that migratory birds are keen to eat fruits rich in antioxidants, which counteract these harmful molecules. Their experiments also demonstrated that the antioxidant vitamin E can enter mitochondria in the flight muscles of lab-raised birds, but only those trained to fly. This potentially counteracts the oxidative stress even at the level of the tiny organelle. Understanding more fundamentally how mitochondria provide birds with additional energy without overproducing reactive oxygen species is “a necessary next step” in this line of research, McWilliams said.

Today, Mesquita has moved on from birds to humans. Whether studying migratory birds at the subcellular level has any real applications for people is a matter of debate, but mitochondria are important in human aging, which is what Mesquita studies now. He still wonders whether a human exercise program, or even a drug, could be developed to increase the overall number and efficiency of mitochondria — effectively remodeling them as in birds.

Whether that’s possible or not, he’s become convinced that “mitochondria are the center of the universe,” he said, quoting a colleague. With the development of better tools to study the organelles, it has become increasingly apparent that many physiological adaptations and diseases come down to mitochondrial functioning. From human exercise to bird migration, “I think it’s all connected,” he said.