The mitoNEET Ligand NL-1 Increased Adiponectin Levels in Mice Via Bioenergetic Changes

Jared M. Norris*, Werner Geldenhuys and Pushkar Saralkar, Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506

Field (Broad Category): Pharmaceutical Sciences (Health Sciences) 

Student’s Major: Biochemistry 

MitoNEET is an iron sulfur protein located on the outer mitochondrial membrane and functions as redox and pH sensor for mitochondrial bioenergetics. This protein belongs to the zinc finger protein family, but contains 2Fe-2S clusters. Our previous data show that use of mitoNEET ligands can be neuroprotective in both traumatic brain injury as well as cerebral stroke. Overexpression of mitoNEET in obese mice, led to an improved metabolism, primarily attributable to the signaling from adiponectin. In this study, we hypothesized that the mitoNEET ligand NL-1 is neuroprotective by increasing adiponectin levels in mice. C57BL/6 mice were treated with NL-1 at 10 mg/kg i.p. for two weeks, and the levels of serum adiponectin were measured. We also evaluated the effect of NL-1 on mitochondrial function in a neuronal N2A cell culture model using the Seahorse BioFlux analyzer. We found in this study that mice treated with NL-1 for two weeks led to increased levels of serum adiponectin. Additionally, we found that the neuronal cells treated with NL-1 led to improved mitochondrial function, as observed via improved ATP synthesis. Also, cells treated with NL-1 showed a significant reduction in reactive oxygen species levels. Taken together, this suggests that the mitoNEET ligand NL-1 may have positive effects on mitochondrial metabolism via signaling from adiponectin. 

Funding: 

Program/mechanism supporting research/creative efforts: WVU 497-level course