A brain fit for the 21st century is one that understands – and respects – its own bioenergetic foundations

by Hannah Critchlow  BIO

A coloured transmission electron micrograph of a steroid-secreting cell of the zona fasciculata. The mitochondria (red) are surrounded by smooth endoplasmic reticulum (blue). Photo by Jose Calvo/Science Photo Library

is a neuroscientist, author and broadcaster based at Magdalene College at the University of Cambridge, UK. Her books include The Science of Fate (2019), Joined-Up Thinking (2022) and The 21st Century Brain (2026).

Edited byNigel Warburton

About 2 billion years ago, evolution performed an improbable experiment. A larger ancestral cell engulfed a smaller bacterium. It should have been a meal. Instead, it became a merger. The bacterium survived inside its host, and together they forged one of the most consequential partnerships in the history of life. The host offered shelter and access to oxygen. The bacterium supplied something revolutionary: a vastly more efficient way to generate energy.

From this intimate alliance emerged the eukaryotic cell – and with it, the possibility of complex life. Every plant, animal and thinking being traces its lineage back to that ancient symbiosis. Our capacity for reflection, imagination and doubt rests upon what was once a free-living microbe. We call these descendants mitochondria.

They persist in nearly every cell of our bodies, hundreds to thousands at a time. In total, we carry an estimated 10 million billion of them – collectively accounting for roughly a 10th of our body mass. Red blood cells are the exception: they lack mitochondria, which maximises oxygen transport. Almost every other cell depends on them absolutely. Neurons are especially demanding hosts. Each contains thousands of mitochondria, occupying up to 40 per cent of its volume.

These rod-shaped structures are often described as the cell’s powerhouses. Through aerobic metabolism, they generate most of the chemical energy that keeps cells alive and functioning – the molecular fuel that sustains every biological process.

Although the brain represents just 2 per cent of body weight, it consumes about 20 per cent of our energy at rest. Every perception, memory, emotion and idea is metabolically expensive. Thought itself is an energy-hungry act. Weight for weight, our brains are more mitochondrial than neural. This is more than a biological curiosity. It suggests that cognition is inseparable from metabolism – that the mind is not only shaped by networks of neurons but by networks of energy.

When I was a doctoral student two decades ago, mitochondria were presented as static ‘powerhouses’ of the cell, dutiful but conceptually dull. Today, they are at the centre of a scientific reappraisal. Far from being passive batteries, mitochondria are dynamic regulators of cellular life and death, stress responses, inflammation and ageing. Increasingly, they are implicated in how clearly we think, how resilient we feel, and how well we adapt to uncertainty.

The scientific picture has shifted dramatically over the succeeding 20 years. In my own work as a neuroscientist, author and broadcaster, I have watched mitochondria move from the margins of biology to the centre of an emerging conversation about how modern lives shape our brains. As I explore in my book The 21st Century Brain: Using Cutting-Edge Neuroscience to Help Us Navigate the Future (2026), a quiet energy crisis may be unfolding within modern bodies.

Sedentary lifestyles, chronic stress, environmental pressures and nutritional excess can paradoxically strain the very systems that sustain cellular power. If cognition is metabolically grounded, then the quality of our thinking may depend – more than we have yet recognised – on the vitality of these ancient symbionts.

To understand how we fuel our thoughts is to revisit the evolutionary bargain that made thought possible in the first place. The story of mitochondria is not simply a tale of cellular energetics. It is a reminder that intelligence emerged from cooperation – and that the clarity of our minds may hinge on the health of an alliance forged billions of years ago.

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The idea that intelligence might depend on energy sounds almost trivial. Of course the brain requires fuel. Yet only recently has it become possible to observe, in living humans, the energetic machinery underlying thought.

At Imperial College London, the molecular psychiatrist Oliver Howes and colleagues used positron emission tomography (PET) scanning to map the distribution of mitochondrial complex I (MC-I) – the largest enzyme in the oxidative phosphorylation pathway that produces ATP, the........

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