Enhanced Mitochondrial Biogenesis Promotes Neuroprotection

News Release, World Mitochondria Society, Berlin - Germany – March 3, 2023

Transmission electron microscopy images of H7-hRGCWT and H7-hRGCE50K after 24 h DMSO or BX795 (1 μg/ml) treatment, at 49000X magnification. Asterisks represent mitochondria. 

Mitochondrial dysfunctions are widely afflicted in central nervous system (CNS) disorders with minimal understanding on how to improve mitochondrial homeostasis to promote neuroprotection.

Surma et al. have used human stem cell differentiated retinal ganglion cells (hRGCs) of the CNS, which are highly sensitive towards mitochondrial dysfunctions due to their unique structure and function, to identify mechanisms for improving mitochondrial quality control (MQC).

They showed that hRGCs are efficient in maintaining mitochondrial homeostasis through rapid degradation and biogenesis of mitochondria under acute damage.

Using a glaucomatous Optineurin mutant (E50K) stem cell line, they showed that at basal level mutant hRGCs possess less mitochondrial mass and suffer mitochondrial swelling due to excess ATP production load.

Activation of mitochondrial biogenesis through pharmacological inhibition of the Tank binding kinase 1 (TBK1) restores energy homeostasis, mitigates mitochondrial swelling with neuroprotection against acute mitochondrial damage for glaucomatous E50K hRGCs, revealing a novel neuroprotection mechanism.

Acess full article.

Image credit: © Surma et al. Commun Biol (2023).