How & Why Mitochondria Make Their Own Fat | Sara Nowinski | 263

Nov 18, 2025

Sara Nowinski, an Assistant Professor focused on mitochondrial biology, dives into the fascinating world of mitochondria and their ability to synthesize their own fatty acids. She explains the evolutionary significance of this process and how disrupting it can lead to severe health issues. The conversation also highlights the crucial role of lipoic acid in mitochondrial function and its implications in metabolic diseases. Furthermore, Sara emphasizes the importance of studying rare mitochondrial disorders, shedding light on their impact and the need for effective treatments.

Ask episode

AI Snips

Chapters

Transcript

Episode notes

INSIGHT

Free Lipoic Acid Can't Replace Endogenous Lipoylation

Free lipoic acid cannot be attached to mitochondrial enzymes because transferases move it directly from the acyl carrier protein.
Exogenous lipoic acid supplements don't restore protein lipoylation for mitochondrial enzymes.

INSIGHT

MitoFAS Is Required For ETC Integrity

Disrupting early steps of mitochondrial fatty acid synthesis reduces electron transport chain (ETC) complexes and mitochondrial respiration.
This ETC defect is independent of lipoic acid loss and linked to building fatty acids on the acyl carrier protein.

INSIGHT

Longer Mitochondrial Fats Help Build The ETC

Longer fatty acids from MitoFAS interact with ETC assembly factors and stabilize complex assembly.
The acyl carrier protein physically contacts assembly factors that help build large ETC complexes.

Get the Snipd Podcast app to discover more snips from this episode

Get the app

Send us Fan Mail

Mitochondrial fatty acid synthesis is a little-known but essential pathway that supports energy production and metabolic health.

Summary: Dr. Sara Nowinski explains how mitochondria not only burn fuels to make ATP but also synthesize their own fatty acids inside the matrix; this conserved pathway produces lipoic acid (an essential enzyme cofactor) and longer-chain fats required for proper assembly of the electron transport chain, and disrupting it impairs respiration, glucose handling, and insulin sensitivity while enhancing it appears protective against obesity and heart injury.

About the guest: Sara Nowinski, PhD is an assistant professor in the Department of Metabolism and Nutritional Programming at Van Andel Institute in Grand Rapids, Michigan, where since 2021 she has led a lab focused on mitochondrial biology and the mitochondrial fatty acid synthesis (mitoFAS) pathway.

Topics Discussed:

Basic mitochondrial energy production: food → pyruvate/fatty acids → acetyl-CoA → TCA cycle → electron transport chain → ATP
Mitochondrial fatty acid synthesis (mitoFAS): a bacterial-like pathway that builds fats on an acyl carrier protein inside the matrix
Lipoic acid: an 8-carbon fatty acid made only by mitoFAS, covalently attached to key enzymes (e.g., pyruvate dehydrogenase); cannot be rescued by supplements for cofactor use
Longer mitoFAS products (14–16 carbons) stabilize electron transport chain assembly factors, explaining why pathway loss collapses respiration even when lipoic acid is intact
Knocking out mitoFAS causes embryonic lethality, insulin resistance, poor glucose homeostasis, and a rare neurodegenerative disorder (MEPAN syndrome)
Overexpressing the mitochondrial acyl carrier protein protects mice from diet-induced obesity, insulin resistance, and cardiac injury
Muscle cell differentiation fails without mitoFAS, hinting at a role in tissue development and repair

Practical Takeaways:

Supplemental lipoic acid can act as an antioxidant but cannot replace the lipoic acid your mitochondria must make themselves for enzyme function.
Severe impairment of mitochondrial fatty acid synthesis is linked to insulin resistance and metabolic disruption, suggesting mitochondrial health (beyond just biogenesis) matters for glucose control.

*Not medical advice.

Support the show

Health Products by M&M Partners:

SporesMD: Premium mushrooms products (gourmet mushrooms, nootropics, research). Use code 'nickjikomes' for 20% off.
Lumen device: Optimize your metabolism for weight loss or athletic performance. MINDMATTER gets you 15% off.
AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, $100 off AquaTru Carafe, Classic & Under Sink Units; $300 off Freestanding models.
Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app.
KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime)

For all the ways you can support my efforts