MOXI-MTLN : Zap that Fat!

Updated: Feb 2, 2020

A micropeptide encoded by LINC00116 that regulates Fatty Acid Oxidation,

co-discovered by Olson and colleagues (MOXI) and Boudreau and colleagues (Mitoregulin/MTLN).

Original Article :

Makarewich, C. A., Baskin, K. K., Munir, A. Z., Bezprozvannaya, S., Sharma, G., Khemtong, C., … Olson, E. N. (2018). MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid β-Oxidation. Cell Reports, 23(13), 3701–3709.

Original Article :

Stein, C. S., Jadiya, P., Zhang, X., McLendon, J. M., Abouassaly, G. M., Witmer, N. H., … Boudreau, R. L. (2018). Mitoregulin: A lncRNA-Encoded Microprotein that Supports Mitochondrial Supercomplexes and Respiratory Efficiency. Cell Reports, 23(13), 3710-3720.e8.

LINC00116, a long-non-coding RNA that is highly expressed in muscle, finally reveals its true colors. Two back-to-back reports demonstrate that this lncRNA in fact encodes a highly conserved SEP that appears to regulate fatty acid oxidation. While Makarewich et al. propose that MOXI interacts with trifunctional protein HADHA to enhance beta-oxidation, Stein et al. find that MLTN has pleiotropic effects in calcium handling, electron transport, and beta-oxidation.

A year later, Chugunova et al., (2019) PNAS reports similar findings but proposing that MTLN/MOXI interacts with NADH-dependent cytochrome b5 reductase to stimulate the electron transport chain. This is one popular SEP. However, the lack of a unifying mechanism and a consensus on its molecular partner(s) suggest that there is more than meets the eye...

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