Cardiolipin Alterations during Obesity: Exploring Therapeutic Opportunities

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  Figure 1. Main processes and proteins regulated by cardiolipin. Mitophagy and apoptosis—Translocation of cardiolipin (CL) to the mitochondrial outer membrane is involved in signaling the execution of mitophagy (in interaction with LC3) and apoptotic cell death (in interaction with BAX and BAK). Bioenergetics—CL is essential for mitochondrial ATP production through the regulation of ADP/ATP carrier (AAC) activity, the assembly of ATP-synthase and respiratory complexes and super complexes. In addition, CL has been shown to interact with protons and to facilitate their transfer from the respiratory chain to the ATP-synthase for optimal coupling. Biogenesis—Mitochondrial biogenesis relies on the incorporation of mitochondrial proteins through TOM and TIM translocases, whose proper function necessitates CL. Cristae structure—CL enrichment in cristae and its interaction with proteins involved in cristae structure such as OPA1 and the ATP-synthase confer specific physical properties to the inner membrane and favor its strong curvature, which optimize mitochondrial ATP production. Dynamics—CL influences mitochondrial dynamics through its interaction with GTPases involved in mitochondrial fusion or…

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  Figure 2. Summary of published alterations of cardiolipin in obese patients or rodents. CL: cardiolipin, NAFLD: non-alcoholic fatty liver disease, NASH: non-alcoholic steatohepatitis, ND: not determined. References, in order of citation: (Palavicini et al., 2020) [5], (Peng et al., 2018) [6], (Nassir & Ibdah, 2014) [91], (Koliaki et al., 2015) [92], (Aoun et al., 2012) [93], (Jha et al., 2018) [95], (Sullivan et al., 2017) [96], (Ruggiero et al., 2011) [9], (Szeto et al., 2016) [10], (Kume et al., 2007) [100], (Eirin et al., 2017) [101], (Lange et al., 2017) [112], (Ritov et al., 2005) [8], (Fajardo et al., 2015) [121], (Fajardo et al., 2017) [122], (Powell-Wiley et al., 2021) [103].