How Mitochondria Control Your Metabolism | Dr. Jared Rutter

Episode of Huberman Lab · September 7, 2026 · 2 h 4 min

Biochemist Jared Rutter explains to Andrew Huberman how mitochondria allocate cellular resources between energy and growth, shaping aging, heart failure, and cancer.

Summary

Jared Rutter, professor of biochemistry at the University of Utah and Howard Hughes Medical Institute investigator, joined Andrew Huberman to reframe metabolism as the sum of the metabolisms of roughly 30 trillion individual cells rather than a single whole-body rate. Rutter described mitochondria as descendants of an engulfed bacterium whose endosymbiosis enabled complex eukaryotic life, noted that mitochondria retain a circular genome inherited exclusively from the mother, and explained that mitochondria differ between cell types and can even differ within a single cell, citing work from Craig Thompson's group at Sloan Kettering.

Much of the conversation centered on what Rutter called the resource allocation decision made at pyruvate: a cell can import pyruvate into mitochondria to be oxidized for ATP, or divert it toward biomass for building new cells. He recounted how his laboratory, working with fly geneticist Carl Thummel and using yeast, fly, and human cell systems, identified MPC1 and MPC2 as the long-sought mitochondrial pyruvate carrier, published in 2012 simultaneously with Jean-Claude Martinou's group in Geneva. Deleting the MPC in mouse heart, he said, does not kill cells by starving them of ATP—they burn fat instead—but drives cardiomyocytes toward growth, producing a dilated heart and fatal heart failure.

Rutter also discussed lactate as a legitimate fuel rather than mere waste, the prioritization of fatty acid burning because free fatty acids are acutely toxic, and the Warburg effect, which he argued reflects not broken mitochondria, as Otto Warburg concluded in the 1920s, but cancer cells allocating resources toward building rather than burning. He argued that the central difficulty of cancer therapy is that tumor cells are self and are under evolutionary pressure, and predicted that combination regimens targeting the specific mutational and metabolic landscape of an individual tumor—analogous to triple therapy for HIV—offer the best route to something approximating cures.

Huberman pressed on speculative extensions: whether tumors could be understood with the same "adaptive logic" applied to viruses, whether humans are effectively vehicles for their microbiota, whether cancers should be classified by cellular metabolism rather than anatomical site, and whether metabolism could one day be imaged at cellular resolution in living people. Rutter called cellular-resolution metabolic imaging a genuinely hard problem of both spatial resolution and finding a measurable surrogate, and said scent-based detection of disease is plausible because odors are chemistry reflecting altered metabolism. Rutter also endorsed the widely held hypothesis that mitochondria with excess energy generate reactive oxygen species that damage proteins and DNA and contribute to aging.

Chapters

2:32
Metabolism as the sum of cells
Rutter argues that whole-body metabolism is the aggregate of the metabolism of roughly 30 trillion individual cells, each making its own choices about nutrients.
5:38
Aging, damage accumulation, and mitochondria
Huberman asks why energy declines with age and Rutter describes mitochondria becoming less energized and damage accumulating at the cellular level.
8:36
Endosymbiotic origin and mitochondrial inheritance
Rutter explains mitochondria as domesticated bacteria that enabled complex life, retaining a circular genome inherited entirely from the mother.
18:18
Spatial distribution and cell-specific mitochondria
The two discuss mitochondria trafficking to neuronal terminals and crawling immune cells, and how cardiomyocyte and intestinal stem cell mitochondria are wired differently.
25:59
Insulin, fat cells, and nutrient signaling
Rutter describes how hormonal signals after eating instruct different cells differently, with adipocytes converting glucose to stored fat.
30:52
Glycolysis, pyruvate, and the burn-or-build bifurcation
Rutter walks through glucose to pyruvate and the pivotal decision to oxidize pyruvate for ATP or convert it into biomass.
39:41
Cancer, viruses, and evolutionary logic
Huberman asks whether tumors can be understood like viruses; Rutter explains that cancer evolves within a single host and that FDG-PET reveals tumors' glucose appetite.
48:36
Microbiome and the question of who serves whom
Huberman raises the idea that humans are vehicles for their microbiota and Rutter concedes he cannot disprove it.
51:44
Discovering MPC1 and MPC2
Rutter recounts how genetics in yeast, flies, and human cells identified the mitochondrial pyruvate carrier, published in 2012.
1:00:09
Fasting, glucagon, and fuel preferences of heart and brain
Rutter explains glucagon's release of stored fat, the heart's omnivorous fuel use, and the brain's dependence on glucose.
1:07:03
MPC deletion, heart failure, and cell identity
Deleting MPC in the mouse heart produces dilated cardiomyopathy through misallocation toward growth, prompting discussion of cell identity and size versus function.
1:24:29
Lactate as fuel and energy prioritization
Rutter reframes lactate from waste product to important fuel and explains why cells burn fatty acids first.
1:31:32
The Warburg effect and cancer metabolism
Rutter explains that reduced oxygen consumption in tumors reflects building rather than broken mitochondria.
1:36:18
Cancer therapy, resistance, and combination drugs
Rutter describes why killing cancer without killing self is hard and advocates HIV-style combination therapy based on each tumor's biochemistry.
1:48:31
Imaging metabolism and disease detection by scent
Huberman imagines subcellular metabolic imaging; Rutter discusses the technical obstacles and the plausibility of scent-based disease detection.

Key points

What was said, by whom, with the exact words. Timestamps jump to the moment.

Jared Rutter
Rutter argues that whole-body metabolism is the aggregate of the metabolism of each of roughly 30 trillion cells.
“The metabolism of our body is really the sum total of the metabolism of each one of our 30 trillion cells or so”
Listen from 3:19 · Cellular metabolism
Jared Rutter
Rutter says mitochondria almost universally become less energized and less effective with age, though the reasons remain largely unclear.
“it's almost... universally the case that mitochondria become less energized, less effective, let's say, as we age”
Listen from 6:36 · Aging
Jared Rutter
Rutter argues that the endosymbiotic origin of mitochondria is the only model scientists have good reason to believe and that complex life could not have arisen without it.
“I think that's the only model that I think any of us as scientists have any good reason to believe”
Listen from 10:32 · Endosymbiosis
Jared Rutter
Rutter explains that because sperm cytoplasm does not enter the egg, mitochondrial DNA is inherited entirely from the mother.
“So the mitochondrial genome of you came completely from your mother. Mine came completely from my mother”
Listen from 16:23 · Mitochondria
Jared Rutter
Rutter says mitochondria congregate at the leading edge of a crawling cell where ATP demand is highest.
“mitochondria will congregate at that leading edge where that ATP is being consumed to make ATP right there so it can be used”
Listen from 19:10 · Mitochondria
Jared Rutter
Rutter cites work from Craig Thompson's group showing a single cell can contain two functionally distinct populations of mitochondria.
“in one cell, you can have two different kinds of mitochondria that have two different functions, and they're distinct in one cell”
Listen from 23:32 · Mitochondria
Linked moment · 27:55Skip to 27:55 using a listen link in the info box.
Jared Rutter
Rutter describes insulin as a signal telling adipocytes to take up glucose and convert it to fat for long-term storage.
“when they see insulin, what they do is they turn on a protein, they start making a protein that will cause glucose to be taken up into that adipocyte”
Listen from 27:55 · Insulin
Jared Rutter
Rutter frames pyruvate as a bifurcation point where food is either converted to energy or to biomass.
“Food can either be converted to energy. or it can be converted to biomass”
Listen from 33:53 · Cellular metabolism
Jared Rutter
Rutter explains that FDG-PET detects cancer because tumors take up large amounts of glucose.
“So the reason we do FDG-PET is to see the cells where in the body is taking up a lot of glucose and tumors take up a lot of glucose”
Listen from 38:50 · Positron emission tomography
Jared Rutter
Rutter argues cancer undergoes the same evolutionary process as viruses but confined within a single host, with very little evidence that cancer is infectious.
“There's very little evidence that cancer is infectious”
Listen from 43:19 · Cancer
Andrew Huberman
Huberman raises the unsettling hypothesis that humans function as vehicles for the propagation of their microbiota.
“there is this one model of all of this that's very purely biological that we are just shuttles for the microbiota”
Listen from 49:28 · Gut microbiome
Jared Rutter
Rutter says the existence of a mitochondrial pyruvate carrier had been known for 60 or 70 years before the protein was identified.
“It's been known for 60 or 70 years that mitochondria must have a carrier to enable pyruvate to get in, but it was not identified what that protein was”
Listen from 53:25 · Mitochondrial pyruvate carrier (MPC1/MPC2)
Jared Rutter
Rutter says his lab's motivation to study mitochondria was the realization that the functions of many mitochondrial proteins were unknown.
“the realization that many of the proteins that make up mitochondria, that do the stuff that mitochondria do, we don't know what their functions are”
Listen from 54:09 · Mitochondrial pyruvate carrier (MPC1/MPC2)
Jared Rutter
Rutter says cells continuously monitor their ATP levels and mount strong responses when energy is depleted.
“every cell, almost all cells know how much usable energy ATP they have all the time”
Listen from 1:00:50 · Cellular metabolism
Jared Rutter
Rutter states that in a normal human, roughly 70 to 80 percent of the energy extracted by heart muscle cells comes from fat.
“I think it's estimated 70% to 80% of the energy extraction that happens in cardiomyocytes and heart muscle cells is happening from fat”
Listen from 1:03:37 · Cellular metabolism
Jared Rutter
Rutter reports that mice lacking MPC in the heart die of dilated heart failure not from ATP shortage but from misallocating resources toward growth.
“it's pretty clear that they don't die from an inability to make ATP. Because they can burn other things to make ATP”
Listen from 1:08:18 · Heart failure
Jared Rutter
Rutter says the MPC discovery required triangulating yeast, fly, and human cell data and could not have been made in any single model organism.
“we could not have made that discovery with any one type of organism. If we just had the yeast data, we wouldn't have figured it out”
Listen from 1:23:51 · Mitochondrial pyruvate carrier (MPC1/MPC2)
Jared Rutter
Rutter says lactate, long viewed as a waste product, is now known to be an important fuel that the heart readily burns.
“lactate is a very important fuel on its own. The heart, for example, is quite good at consuming lactate and burning it”
Listen from 1:26:13 · Lactate
Jared Rutter
Rutter argues cells burn fatty acids first because excess free fatty acids are acutely toxic, whereas excess glucose is toxic chronically.
“most cells, when they have fatty acids, will burn the fatty acids first, probably as a response to, hey, this could kill us”
Listen from 1:30:07 · Lactate
Jared Rutter
Rutter argues that mitochondria in cancer cells are not broken, contrary to Warburg's interpretation, but are very good at making biomass.
“it turns out that mitochondria and cancer cells are not broken. In fact, they're very, very good, not necessarily at making ATP, but at making stuff”
Listen from 1:35:13 · Warburg effect
Jared Rutter
Rutter frames the central challenge of cancer therapy as killing cancer cells, which are our own cells, without killing the rest of the body's cells.
“The challenge for us is to figure out a way to kill those cells which again are our cells, they are us, is to kill those cells without killing the rest of our cells”
Listen from 1:38:16 · Cancer
Jared Rutter
Rutter predicts that combinations of safe, specific drugs matched to a tumor's biochemistry could produce something approximating a cure, analogous to HIV triple therapy.
“it's going to be very hard for that tumor to become resistant to all of those drugs simultaneously. And as a result of that, that might result in something approximating a cure”
Listen from 1:40:12 · Cancer
Jared Rutter
Rutter criticizes the classification of cancers by anatomical site, noting some breast cancers resemble some liver cancers more than other breast cancers.
“there are some breast cancers that are more similar to some liver cancers than they are to other breast cancers”
Listen from 1:44:59 · Cancer
Jared Rutter
Rutter says imaging metabolism at cellular resolution inside a human body is a very difficult problem of both spatial resolution and finding a visible surrogate.
“I should be clear, that's a very difficult problem. The spatial resolution, the ability to see fine enough detail to make out individual cells are even smaller than that”
Listen from 1:50:56 · Cellular metabolism
Jared Rutter
Rutter suggests that scent-based detection of disease is plausible because differing metabolism produces different chemical compounds.
“when a person's doing different metabolism, they're going to be producing different chemicals in different proportions”
Listen from 1:55:47 · Cancer
Jared Rutter
Rutter says it is widely accepted that mitochondria carrying too much energy generate reactive oxygen species that damage DNA and proteins and may contribute to aging.
“when that mitochondria is overpowered, that leads to a state that is very susceptible to generation of these reactive species that end up damaging our genome”
Listen from 1:58:02 · Reactive oxygen species

People

In the conversation

Andrew HubermanAmerican neuroscientist, professor at Stanford School of Medicine and host of the Huberman Lab podcast
Jared RutterAmerican biochemist, professor of biochemistry at the University of Utah and Howard Hughes Medical Institute investigator specializing in mitochondria and metabolism

Discussed

Otto WarburgGerman scientist who observed in the 1920s that cancer cells consume less oxygen than expected, giving rise to the Warburg effect
Mario CapecchiUniversity of Utah geneticist and Nobel laureate who developed knockout mouse technology
Craig ThompsonCancer researcher at Memorial Sloan Kettering whose group reported two functionally distinct mitochondrial populations within one cell
Carl ThummelDrosophila geneticist at the University of Utah who collaborated with Rutter on the MPC discovery
Jean-Claude MartinouGeneva-based scientist whose lab independently published the identification of the mitochondrial pyruvate carrier in 2012
Joshua RabinowitzPrinceton professor referred to by Rutter as Joshua Benowitz, whose work showed lactate is an important circulating fuel
David FajgenbaumPhysician who treated his own Castleman's disease and founded a nonprofit repurposing approved drugs
Justin SonnenburgStanford microbiome researcher who co-authored a study on fermented foods and inflammation
Andy GalpinExercise physiologist cited by Huberman on lactate versus lactic acid
Layne NortonNutrition and exercise scientist cited by Huberman on energy toxicity from excess calories
Achmed KluntenFormer postdoc, now running his own lab at Rutgers, who initiated work on cardiac MPC deletion

Topics

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From the publisher

Dr. Jared Rutter, PhD, Professor of Biochemistry at the University of Utah and Howard Hughes Medical Institute Investigator, is a leading expert on mitochondria and metabolism. He explains how mitochondria produce the energy for your cells to work but also how they regulate cell growth and replication and thereby contribute to health and disease. We also discuss how mitochondria are linked to aging, cancer, and other diseases. Our conversation explores your metabolism as the composite of trillions of individual cells and points to new ways to improve health, avoid, and treat diseases. Show notes: https://go.hubermanlab.com/297-jared-rutter Pre-order Protocols: https://protocolsbook.com Thank you to our sponsors AG1: https://drinkag1.com/huberman Joovv: https://joovv.com/huberman BetterHelp: https://betterhelp.com/huberman Eight Sleep: https://eightsleep.com/huberman Function: https://functionhealth.com/huberman Timestamps (00:00:00) Jared Rutter (00:02:29) Metabolism, Cells; Aging (00:08:36) Mitochondria, Origin & Cell Complexity (00:13:07) Sponsors: Joovv & BetterHelp (00:15:16) Mitochondria Genome, Inheritance (00:18:18) Mitochondria & Spatial Distribution; Cell-Specific Metabolism (00:25:59) Nutrient Energy, Hormones, Fat Cells (00:31:13) Glucose, ATP Conversion, Pyruvate (00:36:41) Cell Choice: Energy or Growth, Cancer; Virus (00:46:02) Sponsors: AG1 & Eight Sleep (00:48:36) Microbiome, Role of Humans (00:51:44) Molecule Discovery Process, MPC1, MPC2 (00:59:42) Cell Resource Sensing, Fasting, Glucagon, Fat Cells; Neurons, Heart (01:07:03) Cell Resource Allocation, MPC, Heart Failure; Disease (01:11:46) Sponsor: Function (01:13:24) Cell Size vs Fuel Balance, Cell Identity & Disease (01:20:43) MPC Discovery, Genetics, Model Systems (01:24:29) Lactate, Oxygen, Exercise; Energy Prioritization Hierarchy (01:31:32) Cancer, Mutations, Metabolism Changes & Warburg Effect (01:36:18) Cancer Challenges & Therapies (01:43:00) Therapy Combinations, Unique Cancer Mutations &…

Summary, chapters and key points were generated from the episode transcript on September 27, 2026. Quotes are checked word for word against the transcript.

Categories: Life Sciences·Medicine·Science