This work highlights the neccessity to explore tissue specific responses to disease and designing therapy according to it. Grateful for the support and contributions from ASWlab, collaborators and @awartiovaara.bsky.social
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#MitochondrialDisease #MuscleBiology #PDK4 #Ophthalmoplegia

5/5 Detailed microscopic analysis using mitoQC by Takayuki Mito shows fiber-specific stalled autophagy/mitophagy in both EOMs and quadriceps.

4/5 PDK4 is highly upregulated in EOMs, inhibiting glucose oxidation and pushing a shift toward fatty acid metabolism.

3/5 EOMs and quadriceps respond remarkably distinctly to mitochondrial stress. Quadriceps activate ISRmt and anabolic pathways; EOMs do not.
#mitochondria #myopathy #stressresponses

2/5 In MMs , the extraocular muscles (EOMs) — the tiny muscles controlling eye movement are the first to weaken, while larger muscles like thigh (quadriceps) remain relatively spared. The mechanisms behind this selective vulnerability have remained elusive.