The mitochondrial L-lactate dehydrogenase affair

The existence of a mitochondrial L-lactate dehydrogenase (m-L-LDH) suggested by Dianzani (1951), was shown by Baba and Sharma (1971) with the enzyme located in the mitochondrial matrix; later Brooks et al. (1999) proposed the intracellular lactate shuttle and in the third millennium the existence of m-L-LDH was definitively been confirmed in mammalian, plant and yeast mitochondria as reviewed by Schurr (2006), Passarella et al. (2008), and Brooks (2009), being its existence finally recognized by inclusion of m-L-LDH in the Mitocarta (http://www.broadinstitute.org/pubs/MitoCarta/index.html). The experimental strategy to be used to show whether and how L-lactate can enter mitochondria to be metabolized is well-established and has been applied to a variety of mitochondria including heart (Brooks et al., 1999; Valenti et al., 2002), liver (Brooks et al., 1999; de Bari et al., 2004), skeletal muscle (Dubouchaud et al., 2000; de Bari et al., 2008; Passarella et al., 2008) plant (Paventi et al., 2007), brain (Schurr, 2006; Atlante et al., 2007; Schurr and Payne, 2007; Hashimoto et al., 2008), and cancer cells (de Bari et al., 2010a; Pizzuto et al., 2012). Thus, it is a matter for considerable surprise that the overwhelming evidence for an m-L-LDH located inside mitochondria is not by now universally accepted (Rasmussen et al., 2002; Sahlin et al., 2002; Ponsot et al., 2005; Gladden, 2007; Yoshida et al., 2007; Elustondo et al., 2013).