The Day Your Cells Run Out of Power: The Real Science Behind ALS — and Why We Lost Eric Dane Too Soon

Yesterday, the world lost Eric Dane to ALS. 

You may know him as Dr. McSteamy — the "charming surgeon" who walked out of a steam-filled bathroom on Grey's Anatomy and into television history (that's where I first saw him). Or as Cal Jacobs, the deeply troubled patriarch of Euphoria. Or simply as a 53-year-old father who looked into a camera not long ago and said, "I have two daughters at home. I want to see them graduate college, get married, maybe have grandkids."

He died on February 19, 2026, surrounded by dear friends, his devoted wife, and his two daughters, Billie and Georgia — who were, by all accounts, the center of his world. I saw the news and it crushed me. 

He had been fighting ALS — amyotrophic lateral sclerosis — for less than a year since his public diagnosis. It started with weakness in his right hand. He thought maybe he'd been texting too much. A few weeks later, it got worse. Nine months of appointments — two hand specialists, two neurologists — before he finally had an answer. And that answer was one of the most devastating in medicine.

There is no known cure for ALS (hopefully that changes). 

But there is an explanation. And understanding it — really understanding it, at the level of biology that textbooks don't usually bother to translate for regular people — is one of the most important things we can do to honor those we lose to this disease.

Many of you have asked me to discuss this. So let's go deep. Let's go to the place where ALS actually begins: inside the cell, inside the engine room, inside the mitochondria.

First — What Even Is ALS?

ALS stands for amyotrophic lateral sclerosis (aka Lou Gehrig's disease).

The Ice Bucket Challenge disease.

It destroys motor neurons — the nerve cells responsible for sending signals from your brain to your muscles. Walking. Breathing. Swallowing. Speaking. All of that is motor neuron territory.

When those neurons die, the signals stop. They waste away.

About 1 in 300 Americans are affected by ALS. The average life expectancy after diagnosis is 3 to 5 years. Some, like Stephen Hawking, beat those odds dramatically. But most don't, unfortunately. 

But here's what most people don't know: the story of ALS isn't just about neurons dying. It's about why they die. And the answer involves the most ancient, alien, and astonishing structures inside your body.

The Mitochondrial role

You've heard it before: "Mitochondria are the powerhouse of the cell." I talk about it all the time! 

But let's actually think about what that means — because it's genuinely mind-blowing.

Mitochondria are not just "power generators." They are, in a very real sense, ancient bacteria living inside you. 

The current story is: about 1.5 billion years ago, a primitive cell engulfed a bacterium. Instead of digesting it, the two formed a partnership. The bacterium became the mitochondrion. It still has its own DNA — separate from yours. It still replicates on its own schedule.

Right now, you have hundreds to thousands of mitochondria in every cell. In your heart muscle cells, up to 5,000. In your neurons — especially your motor neurons — enormous numbers, because those cells are the hungriest in your body.

And here's the thing: your mitochondria aren't just making energy. They're running an electrical operation. Inside the inner membrane, they pump protons like a dam building up water pressure, creating a voltage gradient. That gradient powers a molecular turbine — called ATP synthase — that spins 100 to 150 times per second, assembling molecules of ATP. Every. Second. Of your life.

ATP is the currency of cellular life. No ATP, no life. It's that simple.

Why Motor Neurons Are Playing the Game on Hardest Difficulty

Think about what a motor neuron actually is.

The one controlling your big toe originates in your spinal cord and runs all the way down your leg — sometimes over a meter long. It fires constantly. It has to maintain tight ion gradients across its membrane (sodium rushing in, potassium rushing out, thousands of times per second). It has to shuttle supplies — proteins, organelles, signaling molecules — all the way from the cell body in the spine to the nerve terminal in the muscle, and back again. That shuttle service is called axonal transport, and it's powered entirely by ATP.

It's like running a film production where the director sits in New York and the cameras are in Los Angeles, and every single piece of equipment has to be physically driven back and forth, constantly, without stopping.

That process requires staggering amounts of energy. Motor neurons are, pound for pound, the most metabolically demanding cells in the human body.

They have almost zero margin for error.

Any disruption — any wobble in the energy supply, any crack in the mitochondrial machinery — hits them harder than any other cell type. This is the first piece of the ALS puzzle. Motor neurons are already living on the edge.

The Electron Transport Chain: Where Things Start to Go Wrong

Here's where we get into the real machinery, and it's worth understanding because this is where ALS actually begins to dig its claws in.

Your mitochondria generate ATP through a process called oxidative phosphorylation.

It runs through a series of protein complexes embedded in the inner mitochondrial membrane — called the electron transport chain (ETC).

Think of it as a series of relay runners, passing a baton (electrons) from one to the next, releasing energy at each handoff, which is used to pump those protons and ultimately spin that ATP turbine.

In healthy cells, this process is nearly flawless. Electrons flow through the chain, oxygen accepts them at the end (becoming water), and ATP is made.

In ALS — whether from genetic mutations, environmental stress, aging, or combinations we don't yet fully understand — the relay breaks down. Electrons leak out of the chain prematurely. They collide with oxygen molecules to form superoxide — one of the most reactive, destructive molecules in biology.

This is what's called reactive oxygen species (ROS). You may have heard antioxidants are good for you — this is why. The whole antioxidant industry exists because of these rogue molecules.

In ALS motor neurons, ROS production goes into overdrive. And here's what that does:

• Lipid peroxidation: The fats that make up cell membranes get oxidized, destabilized. Membranes begin to fail.
• Protein misfolding: Proteins get damaged and begin to clump together in toxic aggregates. (This is why the SOD1 protein mutation — found in familial ALS — is so devastating. SOD1 is literally one of the body's primary ROS-neutralizing enzymes. When it mutates, you lose your defense while the attack intensifies.)
• DNA damage: Mitochondrial DNA, much more vulnerable than nuclear DNA, begins to accumulate errors.
• Axonal transport failure: The molecular motors hauling cargo down the axon need ATP. ROS disrupts both the motors and the tracks they run on. Supplies stop reaching the nerve terminal.

And when supplies stop reaching the terminal, degeneration begins there first — at the farthest point from the cell body. This is what neurologists call the "dying back" phenomenon. The neuron dies from the outside in, like a vine shriveling from the tip.

This is why ALS patients often notice symptoms in their hands and feet first. It's not a coincidence. It's a geometric consequence of where the energy supply chain breaks down first.

The Calcium Crisis Nobody Talks About

Here's another layer that most people never hear about, and it is extraordinary.

Motor neurons are bombarded, constantly, by glutamate — the brain's primary excitatory neurotransmitter. Every time a motor neuron fires, glutamate flows. This is normal. This is how the system works.

But glutamate doesn't just trigger an electrical signal. It opens calcium channels. Calcium floods into the cell. Calcium is a critical signaling molecule, but it is also — in high concentrations — a cellular poison.

Your mitochondria are the cell's emergency calcium buffers. When calcium levels spike too high in the cytoplasm, mitochondria absorb it, holding it in reserve until things calm down. They are, in this sense, not just power plants but calcium banks.

Many studies have shown that EMFs can cause significant calcium influx. 

But here's the catastrophic feedback loop in ALS: if the mitochondria are already damaged and struggling to maintain their membrane potential, they can't buffer calcium effectively. Calcium builds up in the cell. This triggers a structure called the mitochondrial permeability transition pore — essentially a panic valve in the mitochondrial membrane — to blow open. When that happens, the mitochondrion releases its contents into the cell, triggering a cascade of cell death signals.

This is called excitotoxicity. The neuron is, in a very real sense, being excited to death.

And once you understand this mechanism, the FDA-approved drug riluzole — one of the few treatments for ALS — makes much more sense. Riluzole works partly by reducing glutamate activity, trying to turn down the excitatory signal before it overwhelms the already-burdened calcium management system.

It extends life by only a few months. It's not enough. But it's a window into the mechanism.

The Redox Tipping Point: When the Cell's Chemistry Tilts the Wrong Way

Let's talk about redox biology, because this concept unlocks something profound about ALS — and about cellular aging in general. This is another thing I talk about all the time! 

"Redox" refers to the balance between oxidation (losing electrons) and reduction (gaining electrons) in a biological system. Every cell exists on a redox spectrum. In a healthy cell, this balance is tightly regulated. Antioxidant systems — glutathione, superoxide dismutase (SOD1 and SOD2), catalase, thioredoxin — continuously neutralize oxidative damage, restoring balance.

In ALS, that balance tips. The oxidative load from leaky electron transport chains exceeds the cell's antioxidant capacity. The cell shifts into a chronically oxidized state.

What does that look like?

• RNA gets damaged. RNA is the messenger that carries instructions from DNA to the protein-building machinery. Damaged RNA means corrupted instructions, which means misfolded proteins.
• Proteins aggregate into the toxic clumps (called inclusions) that are a hallmark of ALS pathology.
• The axonal cytoskeleton — the scaffolding that keeps the long axon structurally intact and allows transport — begins to degrade.

It is, to use a mechanical analogy, as if a factory's quality control department shuts down at the same moment the production line accelerates. Every downstream system begins to fail.

The Body Tries to Compensate — And Burns Itself Out

This part is both fascinating and heartbreaking.

Many ALS patients, long before their diagnosis, begin to exhibit something called hypermetabolism. Their resting energy expenditure goes up. They burn calories faster. They lose weight even when eating normally.

Why? Because their cells are becoming metabolically inefficient. When the electron transport chain leaks and ATP synthesis falters, the body's response is to burn more fuel to produce the same amount of energy. It's like a car with a broken engine running rich — burning more gas per mile just to keep moving.

The body compensates. For a while. But that compensation is itself metabolically costly. It accelerates the depletion of energy substrates. It increases oxidative burden. It's a feedback loop that is, at its core, unsustainable.

This is also why nutrition and metabolic support have become increasingly interesting areas in ALS research and care. If the body is burning hotter, fueling it more efficiently — potentially with substrates that bypass the damaged parts of the electron transport chain — might offer some protection. Ketone bodies, for example, generated during ketosis, can enter the energy production pathway at a different point than glucose, potentially providing ATP even when certain ETC complexes are compromised. This is an active area of investigation, not a cure — but it illustrates how deep the metabolic rabbit hole goes.

It's Not Just Neurons — The Entire Neural Ecosystem Fails

ALS is often described as a motor neuron disease. But that framing undersells how systemic the failure actually is.

Motor neurons don't live in isolation. They exist in a rich ecosystem of support cells — primarily astrocytes and microglia — that perform functions the neurons themselves cannot.

Astrocytes, in a healthy brain and spinal cord, do something extraordinary: they recycle glutamate. After a neuron fires and releases glutamate, astrocytes sweep it up from the synapse, recycle it, and send it back. They are the cleanup crew that prevents excitotoxicity.

In ALS, astrocyte function is compromised. Glutamate clearance slows. The excitatory signal lingers longer than it should. Calcium influx increases. Excitotoxicity worsens. And — remarkably — there is evidence that in ALS, astrocytes may actually begin releasing toxic factors that actively harm the motor neurons they're supposed to support.

Microglia — the brain's immune cells — become chronically activated, driving neuroinflammation. Neuroinflammation has its own metabolic cost, demanding more energy from an already-strained system, generating more oxidative stress, further compromising mitochondrial function.

The result is a feed-forward spiral:

Energy stress → Mitochondrial dysfunction → Calcium overload → Excitotoxicity → Astrocyte failure → Neuroinflammation → More energy stress → Faster neuronal death.

Once this loop gains momentum, it becomes extraordinarily hard to interrupt. This is why ALS, once symptomatic, tends to progress with such terrible speed.

Why Did It Take a Decade for Stephen Hawking, and Less Than a Year for Others?

This is one of the great mysteries of ALS — and one of the most painful.

The average life expectancy following an ALS diagnosis is 3 to 5 years. Hawking lived with the disease for 55 years. Eric Dane died less than ten months after going public with his diagnosis.

We don't fully understand why. But the framework of mitochondrial fragility offers some clues.

ALS is not one disease. It is what's called a "convergent phenotype" — a final common pathway that can be reached from many different starting points: genetic mutations (over 30 different genes have now been implicated), environmental exposures, metabolic vulnerabilities, autoimmune dysfunction. The speed of progression likely depends on:

• Which cell populations are initially most vulnerable
• The baseline mitochondrial reserve of the individual
• The efficiency of their endogenous antioxidant systems
• Systemic metabolic health at the time of disease onset
• The genetic subtype driving the disease

A person with a robust mitochondrial network, high antioxidant capacity, and a disease process affecting only specific motor neuron populations may progress slowly. Someone whose mitochondrial resilience has already been eroded — by aging, metabolic dysfunction, or a particularly aggressive genetic variant — may decline rapidly.

The research is increasingly clear that ALS is not a binary — it is a spectrum of metabolic fragility colliding with a spectrum of biological vulnerability. Which is why understanding the underlying biology matters so much. Not just for understanding death, but for finding interventions that might, someday, interrupt that spiral before it's too late.

Eric Dane: A Man Who Chose to Fight Loudly

When Eric Dane was told he had ALS, after nine months of appointments and mounting symptoms, he didn't retreat.

He told Diane Sawyer he would "fly to Germany and eat the head off a rattlesnake" if doctors told him it would help.

He became a passionate public advocate, speaking before Congress about the need to reauthorize the ACT for ALS law, expanding access to treatments. He partnered with I Am ALS and set a goal of raising $1 billion toward research.

In a guest appearance on Brilliant Minds, playing a firefighter with ALS, he delivered a voiceover so powerful the entire cast and crew gave him a standing ovation for ten minutes after they called cut.

In that scene, he said something that feels, today, like it was spoken directly to us:

"Sometimes the most heroic thing you can do isn't running into the burning building. It's quieter, smaller, but in a way even harder — allowing myself to be rescued, even when I don't want to. For me, this is the bravest thing I've ever done. And it's scary as hell, but it is worth it if it means more time with you."

In one of his final pieces of advice to his daughters, he said simply: "Live now, right now, in the present."

What Happens Inside Those Final Months

Understanding the biology makes the progression of ALS even more comprehensible — and more devastating.

In June 2025, Dane told Diane Sawyer: "My left side is functioning; my right side has completely stopped working." He was already losing function in his left arm, estimating he might lose use of his left hand within months.

This progression maps perfectly onto what we now understand about the disease. As the dying-back phenomenon advances — as axonal transport fails in more and more neurons — the muscles those neurons innervate receive no signal. They don't just weaken. They denervate. And denervated muscle, with nothing telling it to contract, wastes away.

The diaphragm is a muscle too. Controlled by motor neurons. As ALS progresses, respiratory function declines. This is, ultimately, how most ALS patients die — not from neurological catastrophe, but from respiratory failure, as the body loses the ability to draw breath.

The disease doesn't just attack what you do. It attacks the invisible machinery that allows you to exist.

Where Are We Now? What Hope Looks Like.

Let's be honest: there is no known cure. And it makes sense when you look at the damage that's been done to the mitochondria. 

There are only a few approved treatments, and they extend life by months, not years. 

But the science is moving — and the framework described in this post is exactly where the most promising research is concentrating.

Mitochondrial-targeted therapies are in development — compounds designed to stabilize the electron transport chain, reduce electron leak, and protect against ROS production specifically within the mitochondria of motor neurons.

Gene therapy approaches — particularly those targeting SOD1 mutations and the TDP-43 protein that aggregates in most ALS cases — have produced exciting early results. A drug called tofersen has shown real promise for SOD1-related ALS, and antisense oligonucleotide approaches are being tested for other genetic variants.

Metabolic interventions — including caloric support, high-fat diets, and ketone supplementation — are under active investigation as ways to reduce the hypermetabolic burden and supply alternative fuel sources to struggling neurons.

Glial cell targeting — finding ways to restore normal astrocyte function, reduce neuroinflammation, and stop microglia from contributing to degeneration — is another active front.

And perhaps most importantly: earlier diagnosis. Eric Dane's story — nine months of hand specialists and neurologists before getting an answer — is tragically common. As Dane told a congressman in September 2025, the delayed diagnosis often precludes patients from participating in clinical trials, shutting them out of the very interventions that might help them most. Biomarkers that can identify ALS earlier — before significant motor neuron loss — could dramatically change the therapeutic window.

The Last Thing

Eric Dane played a doctor on television.  He spent years on screen saving fictional lives, and spent his last year fighting for his own — and then, with remarkable grace, fighting for everyone else's.

The biology of ALS is merciless. An energy crisis in the most demanding cells in the body. A spiral of mitochondrial failure, calcium overload, redox collapse, and glial dysfunction that, once started, is nearly impossible to stop.

But it is understandable. And understanding it is the beginning of defeating it.

Eric Dane said he didn't think this was the end of his story. And whether or not he could hold onto that hope for himself, he made sure the story continued — for the researchers, for the patients, for the people who will come after him.

"Live now, right now, in the present."

That's what he told his daughters. It's good advice for all of us — and it's also, quietly, the most human response possible to a disease that robs you of your future one cell at a time.

Rest in aloha, Eric Dane. 53 years was not enough.

This post references research on mitochondrial dysfunction, redox biology, calcium signaling, and glial cell pathology in ALS. The science presented reflects current research consensus and should not be interpreted as medical advice.

Picture attributed: https://flickr.com/photos/22007612@N05/36250597985