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Peptides for Inflammation, Immunity and Repair

SS-31

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SS-31 (Elamipretide) and Mitochondrial Function

Safety & scope disclaimer (read once, then move on)

This lesson is informational only. SS-31 (elamipretide) is not a general wellness supplement and shouldn’t be treated like one. In the U.S., an elamipretide product (Forzinity) received FDA accelerated approval for Barth syndrome—a rare mitochondrial disease—under specific criteria.
Nothing here is medical advice or a recommendation to use any drug/peptide.

  • Mitochondria are the cell’s energy factories. But the key detail is where energy is made:

    • The inner mitochondrial membrane is folded into cristae (think: “accordion folds”) to create more surface area.

    • That surface area holds the machinery for oxidative phosphorylation—the main ATP-producing system.

    If the inner membrane is disorganized, leaky, or damaged, energy production gets less efficient. You can have plenty of “fuel” (food) and still feel like the engine runs rough.

  • Cardiolipin is a special phospholipid concentrated in the inner mitochondrial membrane. It helps:

    • maintain membrane curvature (cristae structure),

    • organize respiratory chain complexes into functional assemblies (“supercomplexes”),

    • and support efficient electron transport.

    Here’s the simple version: cardiolipin helps keep the power plant walls stable and the wiring properly arranged.

    When cardiolipin becomes oxidized or disrupted, mitochondrial structure and energy output can suffer.

  • SS-31 (also known as elamipretide, and historically as MTP-131/Bendavia) is a small mitochondria-targeting peptide studied for mitochondrial dysfunction.

    It’s often described as a cardiolipin-targeting peptide that accumulates at/near the inner mitochondrial membrane, where cardiolipin is abundant.

  • Think of SS-31 as a membrane-stability + function modulator rather than a “magic energy shot.”

    Research suggests SS-31:

    • Interacts with cardiolipin-containing membranes and can change membrane surface electrostatics (how the membrane environment behaves).

    • May reduce cardiolipin peroxidation and inhibit cytochrome c’s peroxidase activity (one pathway involved in oxidative damage/apoptosis signaling).

    • Is associated in multiple models with improved mitochondrial structure (cristae) and bioenergetics efficiency.

    The takeaway

    If mitochondria are an engine, SS-31 is being studied less as “more gas” and more as “stabilize the engine parts so the fuel burns cleanly.”

  • Strongest bucket: preclinical + mechanistic

    There’s a large body of cell/animal research showing effects on mitochondrial structure/function and stress signaling.

    Human evidence: mixed, condition-specific

    In primary mitochondrial myopathy, a 24-week randomized study reported that elamipretide did not improve the six-minute walk test or fatigue versus placebo (Class I evidence in that paper).

    • For Barth syndrome, elamipretide received FDA accelerated approval (Forzinity) for improving muscle strength in qualifying patients, with required post-marketing confirmation.

    • Longer-term open-label data in Barth syndrome has been reported, but it’s not the same as a large, definitive randomized outcomes trial.

  • SS-31 is a great teaching tool because it forces you to understand the real bottleneck:

    • Mitochondrial performance is not just “more supplements.”

    • It’s structure + membrane integrity + organization of energy machinery.

    • Cardiolipin is central to that story.

Key takeaways (the “save this” section)

Mitochondria = energy production + signaling, and the inner membrane structure is everything.

  1. Cardiolipin helps keep the energy system organized and efficient.

  2. SS-31 (elamipretide) is a mitochondria-targeting peptide studied for cardiolipin/inner-membrane related mechanisms.

  3. Human outcomes are condition-specific and mixed; FDA accelerated approval exists for Barth syndrome under defined criteria, not general wellness.