Mitochondrial reverse electron transport in myeloid cells perpetuates neuroinflammation

Area of Science:

• Neuroimmunology
• Mitochondrial Metabolism
• Chronic Neurological Disorders

Background:

• Sustained myeloid cell activation is a hallmark of chronic neurological diseases like multiple sclerosis.
• The metabolic drivers of persistent neuroinflammation remain poorly understood.
• Myeloid cell metabolic states influence their activation and function.

Approach:

• A multiomics approach was employed to investigate myeloid cell metabolism.
• The study identified a molecular signature linked to mitochondrial complex I and II activity.
• The role of reverse electron transport (RET) in myeloid cell activation was examined.

Key Points:

• Mitochondrial complex II (CII) and I (CI) activity drives reverse electron transport (RET) and reactive oxygen species (ROS) production.
• RET perpetuates myeloid cell activation and neuroinflammation.
• Blocking RET in myeloid cells demonstrated neuroprotective effects in animal models.

Conclusions:

• Myeloid cell RET is a novel therapeutic target for neuroinflammation.
• Targeting RET may foster neuroprotection in chronic inflammatory central nervous system disorders.
• This research opens new avenues for treating diseases like multiple sclerosis.