A great number of proteins
A great number of proteins entering the nucleus possess a characteristic nuclear localization sequence (NLS) in their primary structure. One of such sequences is the KKKGK motif . It is present in all known muscle (but not liver – except human liver) FBPase sequences (human, rabbit, rat and mouse), and it could potentially act as an NLS. Although the primary structure of pig muscle FBPase has not yet been determined, all muscle FBPases are characterized by a very high degree of homology (99%) and identity (95%). Therefore the same NLS in pig muscle FBPase might be expected.
In skeletal muscle, FBPase has been located on both sides of the Z-line . Heart muscle, like skeletal muscle, is considered a striated muscle. Nonetheless, differences in metabolic pathways and their regulation between these two types of muscle are well documented; therefore, different subcellular localization and different physiological role of FBPase in skeletal and heart muscle may be expected.
Introduction Fungi have a very flexible metabolism that enables them to live in a variety of environments and to use diverse carbon sources. They can grow on a range of carbohydrates using glycolysis but are also able to grow on two-carbon compounds, fatty acids, or other sources of tricarboxylic AR-C155858 (TCA) cycle intermediates, thereby requiring gluconeogenesis. Glycolysis and gluconeogenesis are two opposite pathways for glucose metabolism (degradation or biosynthesis of glucose), and fungi have to adapt their carbon metabolism according to the available carbon source. Regulation of the enzymes involved is of great importance to avoid futile cycling between the degradation (glycolysis) and biosynthesis (gluconeogenesis) of sugars. Phosphoenolpyruvate carboxykinase (PCK-1) and fructose-1,6-bisphosphatase (FBPase-1) are the key enzymes of the gluconeogenic pathway. PCK-1 catalyzes an early step converting oxaloacetate to phosphoenolpyruvate. FBPase-1 catalyzes the final step in hexose monophosphate formation by dephosphorylating fructose-1,6-biphosphate to yield fructose-6-phosphate. It has been shown that the expression of these two enzymes is controlled by two zinc cluster transcription factors called RSE2 and RSE3 in P. anserina (Bovier et al., 2014, Sellem et al., 2009), ACUK and ACUM in A. nidulans (Hynes et al., 2007, Suzuki et al., 2012). In N. crassa, the orthologs of these transcription factors (AOD2 and AOD5) also control the expression of pck-1 but not of fbpase-1 (Qi et al., 2017). Surprisingly, in these three species, these transcription factors that are highly conserved, are also required for the expression of the alternative oxidase, AOX (Chae et al., 2007b, Sellem et al., 2009, Suzuki et al., 2012). AOX is a mitochondrial non-proton-pump enzyme of nuclear origin that is able to receive electrons from reduced ubiquinone and to catalyze the reduction of oxygen to water. AOX is found in plants, many fungal species, several protists, some animal phyla and certain bacteria (McDonald, 2008). In most fungi aox transcripts are undetectable, or present at very low levels, under classical growth conditions but become expressed when the cytochrome respiratory chain is restricted by inhibitors or by mutations (Chae et al., 2007a, Lorin et al., 2001, Suzuki et al., 2012). In response to such mitochondrial electron transport chain inhibition, AOX bypasses respiratory complexes III and IV. It is believed to contribute to the maintenance of the tricarboxylic acid (TCA) cycle turnover and to act as an overflow for electron transport, preventing the deleterious oxidative stress associated with the increased generation of mitochondrial reactive oxygen species (ROS). In N. crassa and A. nidulans the orthologs of RSE2 and RSE3 have been shown to bind constitutively to DNA, as a heterodimer, by their N-termini (Chae et al., 2007a, Qi et al., 2017, Suzuki et al., 2012). Thus, it appears that the activation of these transcription factors is achieved by communication of an unknown signal(s) to the nucleus when cells are exposed to specific conditions. The identity of the signal(s) is crucial to the understanding of these regulatory pathways, as is the potential biological significance of this unexpected co-regulation of AOX and gluconeogenic enzymes.