Cardiolipin remodeling by ALCAT1 links mitochondrial dysfunction to Parkinson’s diseases

https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12941

Chengjie Song  Jun Zhang  Shasha Qi  Zhen Liu  Xiaoyang Zhang  Yue Zheng  John‐Paul Andersen  Weiping Zhang  Randy Strong  Paul Anthony Martinez  Nicolas Musi  Jia Nie Yuguang Shi

• Parkinson's disease's (PD) causes remain elusive, but oxidative stress, mitochondrial dysfunction, and defective mitophagy are all considered as the primary pathogenic mechanisms.
• Cardiolipin (CL) is a phospholipid which is almost exclusively located in the inner mitochondrial membrane, where it is biosynthesized.
• ROS-induced damage of CL  is implicated in the pathogenesis of PD, but the mechanism remains unclear.
• The authors induced PD in a mouse model, induced by MPTP (a chemical that caused PD when injected, and has been used to study disease models in various animal studies). They oxidative stress, mtDNA mutations, and mitochondrial dysfunction in the midbrain.
• Then, they ablated  the ALCAT1 gene and treated mice with MPTP. This prevented MPTP‐induced neurotoxicity, apoptosis, and motor deficits and mitigated mitochondrial dysfunction.
• Mitophagy, which removes dysfunctional mitochondria, is also compromised in PD. The pharmacological inhibition of ALCAT1 significantly improved mitophagy, by stimulating the recruitment of Parkin to dysfunctional mitochondria and their association.
• These results show that ALCAT1 may be a promising drug target in the treatment of PD.