The Mitochondria Is the Powerhouse of the Cell—And Maybe Your Mood, Scientists Say

3 min readHere’s what you’ll learn when you read this story:Mitochondria have spent decades typecast as the cell’s fuel tanks, but a new review argues that in the brain, they set the conditions that determine what neural circuits can do.The researchers propose that brain mitochondria work in two complementary modes: a long-timescale “baseline” mode that keeps neurons and circuits primed, and an “activity-evoked” mode that delivers energy and signaling molecules on demand when a circuit fires.In animal studies, boosting mitochondrial function in specific brain regions has reduced anxiety-like behavior, hinting that anxiety may be partly a bioenergetic problem.Having a reputation for fueling and refueling cells earned mitochondria their reputation as “powerhouses of the cell.” They take the products of glucose breakdown, along with fatty acids in some cell types, and use them to crank out ATP (adenosine triphosphate), the molecule that powers nearly everything cells do. What no one knew back in high school biology was that mitochondria are capable of so much more.Besides powering cells with energy, mitochondria in the brain are linked to various functions that influence cognition and behavior. Recently, an international team of researchers who reviewed many previous studies found a link between these organelles and learning, memory, reward, motivation, and anxiety. Synthesizing more than 250 studies, the team argues that mitochondria have dual modes of support in the brain besides recharging cells. What the researchers call baseline mitochondrial support keeps neurons and neural circuits operating and primed to respond. Activity-evoked support is the on-demand version: when a circuit fires, nearby mitochondria ramp up locally, supplying both the energy and the signaling molecules neurons need to keep transmitting.“Distinguishing these two modes helps to explain how behavioural modulators, including stress hormones, immune activity and metabolic signals, can shape behaviour by altering either baseline mitochondrial control of circuit readiness or activity-evoked mitochondrial support during circuit engagement,” the researchers wrote in a review recently published in Nature Reviews Neuroscience.Mitochondria used to be vaguely associated with behavior and cognition, but more and more evidence has revealed them as the force behind much of the brain activity that influences our learning, memory, reward, reinforcement, motivation, and the presence or absence of anxiety in different situations. Both learning and memory are metabolically demanding. They depend on synapses, the junctions where one neuron passes a chemical signal across a 20-nanometer-wide gap to the next, and entire neural circuits being able to adapt immediately. The mitochondria near synapses make adaptation easier with metabolic support on demand. Mitochondria on both sides of a synapse—in the sending terminal and the receiving branch—appear to coordinate their activity, and they can remodel themselves within minutes.Some parts of the learning process that benefit from mitochondrial involvement are reward and reinforcement. Reinforcement (learning which actions are worth repeating based on how they turn out) requires neurons to continually retune the signals they send across synapses. Mitochondria keep these neurons functioning and prepared for changes. High trait anxiety tends to go hand-in-hand with lower motivation, and it’s associated with elevated risk for stress-related conditions including depression. In rodents, natural genetic variation in mitochondrial function tracks with how anxious an animal is, and in experiments, improving mitochondrial function in key reward regions reduced anxiety-like behavior.Brain mitochondria can also be modulated by both internal and external factors affecting behavior and cognition. Hormones, immune molecules, and metabolic signals can all shift what mitochondria produce, and that in turn changes the neurotransmitter signal one neuron sends to the next. The traffic runs both ways: mitochondrial changes feed back into metabolic and immune responses. This can affect metabolic and immune responses. External factors ranging from diet to stress to psychotropic drugs can also have that type of effect, with psychological stress being an especially strong modulator that forces rapid changes depending on the brain region and the type of stressor. Some stressors reach all the way down to gene expression, altering the production of the proteins mitochondria are built from.“[Our] framework places mitochondria at the core of circuit and behavioural neuroscience,” the researchers said, "shifting the emphasis from circuit architecture alone to the mechanisms through which mitochondria set baseline circuit readiness and enable adaptive recruitment during behaviourally relevant activation.”Elizabeth Rayne is a creature who writes. Her work has appeared in Popular Mechanics, Ars Technica, SYFY WIRE, Space.com, Live Science, Den of Geek, Forbidden Futures and Collective Tales. She lurks right outside New York City with her parrot, Lestat. When not writing, she can be found drawing, playing the piano or shapeshifting.