GDF15 modifies NAD+ salvage pathway and dampens immune response in mitochondrial disease

In Deletor mice with mitochondrial muscle disease, GDF15 inactivity upregulated NMRK2, boosting NR-to-NMN conversion and NAD+ production in skeletal muscle.

• Why it matters: The mitochondrial integrated stress response includes early systemic metabokines, but GDF15’s role in local muscle redox control and immune changes was unclear.
• What they did: The study inactivated FGF21 and/or GDF15 in Deletor mice and measured effects on skeletal muscle enzymes, NAD+ salvage via NMRK2, glutathione homeostasis, and immune cell invasion.
• The result: GDF15 inactivity increased immune cell invasion in muscle, and this was aggravated when FGF21 was also lost, implying synergistic anti-inflammatory control alongside redox regulation.

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