FBP2—A New Player in Regulation of Motility of Mitochondria and Stability of Microtubules in Cardiomyocytes

Abstract

Recently, we have shown that the physiological roles of a multifunctional protein fructose 1,6-bisphosphatase 2 (FBP2, also called muscle FBP) depend on the oligomeric state of the protein. Here, we present several lines of evidence that in HL-1 cardiomyocytes, a forced, chemically induced reduction in the FBP2 dimer-tetramer ratio that imitates AMP and NAD+ action and restricts FBP2–mitochondria interaction, results in an increase in Tau phosphorylation, augmentation of FBP2-Tau and FBP2–MAP1B interactions, disturbance of tubulin network, marked reduction in the speed of mitochondrial trafficking and increase in mitophagy. These results not only highlight the significance of oligomerization for the regulation of FBP2 physiological role in the cell, but they also demonstrate a novel, important cellular function of this multitasking protein—a function that might be crucial for processes that take place during physiological and pathological cardiac remodeling, and during the onset of diseases which are rooted in the destabilization of MT and/or mitochondrial network dynamics.

The Effects of Rumen-Protected Choline and Rumen-Protected Nicotinamide on Liver Transcriptomics in Periparturient Dairy Cows

“…Analysis of DEGs revealed a significant increase in the expression levels of FBP and transaminase in the RPC group. Fructose diphosphatase (FBP) can not only regulate the glucose/glycogen synthesis of carbohydrate precursors but can also interact with proteins (such as ATP synthase, HIF1-α and NF-κB) to influence cell-cycle-dependent events, mitochondrial biogenesis and membrane polarization, expression of glycolytic enzymes, induction of synaptic plasticity, and even cancer progression [ 63 ]. Transketolase, a key enzyme of the pentose phosphate pathway that is ubiquitous in all organisms, provides a special connection between glycolysis and the non-oxidation period of the pentose phosphate pathway [ 64 ].…”

Transcriptome Analysis Reveals the Age-Related Developmental Dynamics Pattern of the Longissimus Dorsi Muscle in Ningxiang Pigs

“…In addition, TBX3 (T-box transcription factor 3), an important regulator of muscle and its accessory tissues, exerted an instrumental role in muscle and bone development, and mutations in humans led to Ulnar-mammary syndrome [35]. FBP2 (Fructose 1,6-bisphosphatase 2), in spite of being a key rate-limiting enzyme for gluconeogenesis, protects mitochondria from calcium stress and plays a key role in the regulation of the cell cycle [20,36]. Downregulation of FBP2 significantly elevated basal and compensatory glycolysis in adult myoblasts, upregulated mitochondrial respiration, increased the number of mitochondria in cells, and thus improved cellular metabolism [37].…”

Multitasking Proteins and Their Involvement in Pathogenesis

“…that FBP is not only a regulatory enzyme of glucose/glycogen synthesis but can also influence numerous non-metabolic processes. In the experimental paper "FBP2-A New Player in Regulation of Motility of Mitochondria and Stability of Microtubules in Cardiomyocytes" [8], Pietras et al present several lines of evidence showing that the muscle isozyme of FBP (FBP2) is a regulator of microtubule-dependent dynamics of the mitochondrial network in cardiomyocytes. The chemically induced disruption of FBP2-mitochondria interaction is correlated with an increase in FBP2-Tau and FBP2-Map1B interactions, disturbance of the tubulin network and tubulin-mitochondria interaction, a marked reduction in the mitochondrial trafficking rate, and an increase in mitophagy.…”