Mitochondrial Microproteins - PMC
/PMC/2026
Why It Matters
This paper caught my attention because it reveals an entire hidden layer of mitochondrial regulation we didn't know existed. If you're tracking biomarkers or supplementing for mitochondrial health, this suggests we're still missing fundamental pieces of the puzzle—what we think of as "mitochondrial dysfunction" might involve these microproteins we can't yet measure or target. That said, this is early-stage discovery work, not something actionable yet.
Key Findings
- Small open reading frames (sORFs) in mitochondrial DNA encode functional microproteins that escaped detection because standard gene annotation tools filter out sequences under 100 amino acids
- Several identified microproteins directly interact with respiratory chain complexes (specifically Complex I and Complex V/ATP synthase), affecting ATP production efficiency
- MTLN (mitochondrial lipid nanodomains) microprotein regulates membrane curvature and cristae structure, which determines mitochondrial respiratory capacity
- Some microproteins act as mitophagy regulators, controlling when damaged mitochondria get cleared—potentially explaining why mitochondrial quality control varies between individuals
- Mutations in these microprotein-encoding regions may explain some cases of previously "undiagnosed" mitochondrial disease where nuclear and mitochondrial genome sequencing found nothing
Read the Paper↗PMC12455275