How Mitochondria Control Your Metabolism | Dr. Jared Rutter
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- Dr. Jared Rutter
- Read time
- ~5 min
- Uploaded
- 7 Sept 2026
- Duration
- 2:03:46
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- 386.0K
KEYPOINTS
- 01
Your metabolism is the sum of roughly 30 trillion separate cell-level metabolisms.
Rutter (University of Utah, HHMI) argues that 'calories in, calories out' hides what matters: each cell type runs its own metabolic program suited to its job. A heart muscle cell, a fat cell, a neuron and a gut stem cell take the same fuels and do very different things with them, so health and disease are best understood one cell type at a time.
- 02
Mitochondria do far more than make energy; they also decide how much fuel goes into building new cell material.
The 'powerhouse of the cell' label is incomplete. Mitochondria burn fuel with oxygen to make ATP, the cell's energy currency, but they also supply the building blocks (biomass) a cell needs to grow and divide. Rutter's central theme is this resource-allocation decision between burning fuel and building with it, which happens in every cell all the time.
- 03
Pyruvate is the fork in the road between energy and growth.
Glucose is broken down to pyruvate. Pyruvate can either be carried into mitochondria and fully burned for ATP, which heart cells 'love to do', or be diverted along with other glycolysis intermediates into making new cellular material, which is what the intestinal stem cells that rebuild your gut lining every 5–7 days do.
- 04
Rutter's lab helped identify the mitochondrial pyruvate carrier (MPC1 and MPC2), the gate that lets pyruvate into mitochondria.
Scientists knew for 60–70 years that such a carrier had to exist, but not what it was. Working from mitochondrial proteins of unknown function, his lab and fly geneticist Carl Thummel's lab found the two proteins around 2008–2012, publishing in 2012 at the same time as Jean-Claude Martinou's lab in Geneva. Everything that has mitochondria has MPC1 and MPC2.
- 05
Cells set their energy split by sensing and feedback, not a fixed ratio.
Asked whether heart cells always devote something like 90% of fuel to ATP and 10% to upkeep, Rutter said it is 'definitely not programmed' like a valve with a fixed split. Cells measure their outputs and adjust, an 'adaptive logic' that responds to what the cell and the body need at the moment.
- 06
Hormones carry information about which fuels are available, and cells respond in their own ways.
Insulin (and GLP-1) signals 'I just ate', so cells take up and store or use glucose. Glucagon, a fasting hormone now being combined into some newer GLP-1 drugs, does the opposite: it tells fat cells to release stored fat so the heart and other tissues can burn it.
- 07
Fuel use follows a rough priority order, and excess fatty acids get burned early because they are acutely toxic.
Rutter says there is definitely prioritization, though no strict rules. Excess free fatty acids can be toxic quickly, while high glucose is harmful more chronically. The heart eats a 'dog's breakfast' of fuels (fats, glucose and lactate) so it can keep beating in any metabolic state.
- 08
Lactate is a real fuel, not just a waste product.
When muscle runs short of oxygen during hard exercise, pyruvate can't be burned and is converted to lactate. Lactate was long seen as waste. Rutter cites work over the last 5–10 years from Princeton's Joshua Rabinowitz showing lactate is an important fuel in its own right that tissues like the heart readily burn and that moves energy around the body.
- 09
Cancer cells' mitochondria aren't broken; they are redirected toward building.
In the 1920s Otto Warburg saw that cancer cells use less oxygen than expected and concluded broken mitochondria cause cancer, a view that lasted decades. Rutter says the low oxygen use is real (the Warburg effect), but tumor mitochondria are 'very, very good' at making the material a dividing cell needs rather than burning fuel.
- 10
Overloaded mitochondria are a leading suspect in damage from excess energy and in aging.
A widely accepted but not universal hypothesis holds that when mitochondria are overpowered by too much incoming energy, they produce reactive oxygen species that damage DNA and proteins and cause mutations. Rutter adds that mitochondria become less energized and effective with age almost universally, and that damage building up over time correlates strongly with aging, though the causes are 'largely unclear'.
EXAMPLES
- 01
Mice lacking the pyruvate carrier don't survive.
With knockout technology (developed by Utah Nobel laureate Mario Capecchi), mice missing MPC develop for about 12–13 days, roughly two-thirds of the way to birth, and then die. Flies lacking MPC live but show specific defects, which helped reveal that pyruvate entry into mitochondria was blocked.
- 02
Deleting MPC only in the heart leads to heart failure from a growth decision, not an energy shortage.
In work started by Ahmad Cluntun, a former Rutter postdoc now running a lab at Rutgers, mice with heart-specific MPC loss live for weeks, then die with massively enlarged hearts. They can still make ATP by burning fat. Rutter speculates (his word) that the cells divert glucose into growth, and enlarged heart cells create the same dilated, weak-pumping heart seen in most human heart failure.
- 03
One cell can contain two kinds of mitochondria.
Recent work from Craig Thompson at Memorial Sloan Kettering showed that a single cell can contain distinct mitochondria. In simplified terms, one kind is more biosynthetic (building) and the other more focused on extracting energy and making ATP.
- 04
Mitochondrial DNA comes entirely from your mother.
Mitochondria came from a bacterium that entered an ancestral cell, and they keep their own genome. At fertilization only the sperm's nucleus enters the egg, not its cytoplasm, so all mitochondrial DNA is inherited from the egg. This has implications for how mitochondrial diseases are inherited.
- 05
Cancer is better classified by mutation and metabolism than by organ.
Rutter notes that some breast cancers resemble certain liver cancers more than other breast cancers, because the old system grew out of where surgeons removed tumors. Huberman cites David Fajgenbaum's nonprofit Every Cure, which tests already-approved drugs on individual patients' tumor cells. Rutter adds that a drug killing 99.9% of tumor cells can still fail because the surviving 0.1% regrow the tumor, which argues for combination therapies.
OTHER RELEVANT
- 01
Don't treat 'boosting metabolism' as one dial.
Since each tissue allocates fuel differently, the same intervention can push energy toward burning in one cell type and toward growth in another. Rutter frames future therapies as targeting energy allocation in specific cells, such as the pyruvate fork, rather than whole-body metabolism.
- 02
Excess energy has costs beyond body fat.
Huberman and Rutter agree that chronically taking in too much energy can create downstream biochemical stress, from mitochondrial overload and reactive oxygen species to the acute toxicity of excess fatty acids. This is an argument for avoiding chronic overnutrition. No specific diet or supplement protocol is offered.
- 03
Watch for cell-level metabolic imaging.
Rutter is excited about new tools that measure specific molecules at individual locations inside single cells, mostly in mice and cultured cells for now. Huberman imagines a future body scan showing how each organ's cells split energy between upkeep and growth across a lifetime, which Rutter treats as plausible but not available today.
- 04
Treat 'smelling disease' as intriguing, not diagnostic.
Huberman raises cancer-sniffing dogs and a woman reported to smell Parkinson's. Rutter finds it plausible, since scents are chemistry, but it is poorly understood, correlational and no frontline test.