The Ultimate Mitochondrial Matrix — SS-31 + MOTS-c + NAD+
A comprehensive mitochondrial restoration protocol layering SS-31 (inner membrane repair), MOTS-c (biogenesis activation), NMN (NAD+ substrate), and PQQ (PGC-1α stimulation). Designed for chronic fatigue, exercise performance decline, and mitochondrial age-related dysfunction. The order of administration is critical.
Daily Schedule
Timing and dosage for each step
08:00 AM
20 mg
SS-31 subcutaneous injection. This is the foundation — repair existing mitochondrial membranes before stimulating biogenesis. 20mg/day or 0.25mg/kg body weight.
10:00 AM
10 mg
MOTS-c subcutaneous injection, 2 hours after SS-31. SS-31 first restores membrane structure; MOTS-c then activates AMPK to drive mitochondrial biogenesis. The sequence matters.
08:00 AM
500 mg
NMN 500mg orally with SS-31. Provides NAD+ substrate for the restored and newly generated mitochondria. A repaired ETC with abundant NAD+ maximises ATP production.
08:00 AM
20 mg
PQQ 20mg with breakfast. Stimulates PGC-1α, synergising with MOTS-c for mitochondrial biogenesis. Also acts as an antioxidant protecting newly formed mitochondria.
Protocol Overview
Mitochondrial dysfunction is a primary driver of fatigue, cognitive decline, and accelerated ageing. This protocol addresses it comprehensively across four complementary mechanisms:
Layer 1 — SS-31: Repairs the inner mitochondrial membrane by binding cardiolipin, restoring cristae structure, and recovering electron transport chain efficiency. You cannot build on a broken foundation.
Layer 2 — MOTS-c: Activates AMPK signalling to drive mitochondrial biogenesis — the creation of new, healthy mitochondria. More mitochondria, with repaired structure.
Layer 3 — NMN: Provides NAD+ substrate. A restored electron transport chain with abundant NAD+ substrate produces maximum ATP output.
Layer 4 — PQQ: Activates PGC-1α independently of MOTS-c, providing additive biogenesis stimulation and antioxidant protection of newly formed mitochondria.
Why Sequencing Matters
The critical principle: repair before building. MOTS-c drives biogenesis — creating more mitochondria. But if the existing mitochondrial population is structurally compromised, new mitochondria inherit defective membrane characteristics. SS-31 must precede MOTS-c to establish a healthy mitochondrial template.
Hence the 2-hour gap: SS-31 at 8am, MOTS-c at 10am.
Who This Protocol Is For
- Chronic fatigue syndrome / ME-CFS
- Post-viral fatigue (Long COVID mitochondrial dysfunction)
- Age-related exercise performance decline
- Mitochondrial myopathy (under physician supervision)
- Biohackers targeting cellular energy optimisation
Protocol Duration
Phase 1 (Weeks 1–4): Full protocol — assess tolerance and subjective energy response
Phase 2 (Weeks 5–8): Continue if positive response
Assessment: VO2max testing, subjective energy/fatigue scoring, CoQ10/lactate levels if available
Supporting Interventions
- CoQ10 (ubiquinol) 200mg/day: electron transport chain cofactor
- Magnesium malate 400mg: ATP synthesis cofactor
- Cold exposure: activates PGC-1α independently
- Zone 2 training: primary stimulus for mitochondrial biogenesis
- Avoid alcohol: acute mitochondrial toxin
Disclaimer
SS-31 and MOTS-c are research peptides. NMN is a supplement. This protocol is for educational purposes only.