Idiopathic inflammatory myopathy human derived cells retain their ability to increase mitochondrial function

Area of Science:

• Cellular pathophysiology
• Mitochondrial function
• Skeletal muscle biology

Background:

• Idiopathic inflammatory myopathies (IIMs) are often viewed as autoimmune diseases with passive skeletal muscle involvement.
• Persistent muscle weakness post-inflammation suggests intrinsic skeletal muscle dysfunction.
• Non-immune mediated hypotheses propose intracellular processes as key triggers in IIMs.

Purpose of the Study:

• To investigate mitochondrial function and adaptive capacity in skeletal muscle cells from IIM patients.
• To test the hypothesis of mitochondrial dysfunction in IIM.
• To explore the impact of metabolic stress on IIM skeletal muscle cells.

Main Methods:

• Utilized skeletal muscle-derived cells from healthy controls and IIM patients.
• Assessed mitochondrial function via oxygen consumption rate.
• Imposed metabolic stress by depriving cells of glucose and supplementing with galactose.

Main Results:

• Mitochondria in IIM cells showed reduced respiration in standard glucose-rich medium.
• IIM cells increased mitochondrial respiration when forced to rely on non-glucose metabolism (galactose).
• IIM cells exhibited significantly increased cell death under glucose-free conditions.

Conclusions:

• Mitochondria are functional in IIM; reduced respiration is an adaptive survival response.
• Enhancing mitochondrial metabolic function in IIM cells is detrimental to viability.
• Therapeutic strategies activating mitochondria may harm IIM patients.