The Role of Sarcolipin in Muscle Non-shivering Thermogenesis

The opinion review by Campbell and Dicke questioned if sarcolipin (SLN) is involved in adaptive thermogenesis especially cold adaptation, while agreeing to SLN-mediated heat production (Campbell and Dicke, 2018). Several interesting questions were raised concerning the data implicating SLN in muscle nonshivering thermogenesis (NST). Here, we intend to clarify to the research community that SLN-mediated heat production and adaptive thermogenesis are inseparable. This is because heat production by SLN-SERCA interaction is a biochemical mechanism, whose physiological implication is adaptive thermogenesis. Recent studies from several groups have identified SLN as an important regulator of SERCA pump (Smith et al., 2002; Tupling et al., 2002; Asahi et al., 2003; MacLennan et al., 2003; Vangheluwe et al., 2005; Mall et al., 2006; Morita et al., 2008; Gorski et al., 2013, 2017; Toyoshima et al., 2013; Winther et al., 2013; Gamu et al., 2014, 2015; Montigny et al., 2014; Fajardo et al., 2015). X-ray Crystallographic studies notably from two groups Toyoshima andNissen have provided themolecular details of SLN binding to SERCA, inside the TM groove (Toyoshima et al., 2013; Winther et al., 2013). Studies using genetically altered mouse models provided convincing data that SLN is important for muscle thermogenesis and metabolism (Bombardier et al., 2013; Sahoo et al., 2013; Maurya et al., 2015; Rowland et al., 2015a; Bal et al., 2017). Although the molecular details of SLN function in muscle physiology continues to evolve, there is critical evidence that SLN is a key regulator muscle NST.