Sucrose Synthase

Abstract

Sucrose synthase (SUS: EC 2.4.1.13), a key enzyme in plant sucrose catabolism, is uniquely able to mobilize sucrose into multiple pathways involved in metabolic, structural, and storage functions. Our research indicates that the biological function of SUS may extend beyond its catalytic activity. This inference is based on the following observations: (a) tissue-specific, isoform-dependent and metabolically-regulated association of SUS with mitochondria and (b) isoform-specific and anoxia-responsive interaction of SUS with the voltage-dependent anion channel (VDAC), the major outer mitochondrial membrane protein. More recent work shows that both VDAC and SUS are also localized to the nucleus in maize seedling tissues. Their intricate regulation under anoxia indicates that these two proteins may have a role in inter-compartmental signaling.

The biochemical function of a protein is encoded within its primary sequence and can often be deciphered by simple in vitro assays. The cellular or organismal function of a protein is frequently the same as its biochemical activity. However, for many proteins, the biological function cannot be easily derived based on its biochemical function. This appears to be particularly true when the gene encoding the protein has a history of duplication and is represented by a family of paralogs. In maize and other species, sucrose synthase (SUS) isoforms are almost identical in their catalytic properties.^1,2 However, the characteristic phenotypes of mutants in specific isoforms suggest that the isoforms contribute to vastly different organismal functions.^2–4 Our interest is to identify the range of functions that maize SUS isoforms may have and elucidate the molecular basis of this functional diversity. Although expression divergence and consequent variation in their cellular abundance significantly contributes to this diversity,⁵ other factors such as intracellular distribution, post-translational modifications and interacting partners,^3,4,6,7 seem to be equally critical for the functional diversification of different SUS isoforms.

Our study, spurred by a bioinformatics prediction, opened up a new facet of SUS biology, in that the protein may have organelle-based functions.⁸ Our analysis indicated that two of the three maize SUS isoforms (SH1 and SUS1) partly localize to mitochondria and nuclei, compartments not related to sucrose metabolism. In addition to this isoform-specificity, the compartmentation of SUS isoforms is influenced by developmental as well as environmental cues. Furthermore, its isoform-specific interaction with the voltage-dependent anion channel (VDAC) and an apparent conservation of SUS mitochondrial targeting across plant species suggest that SUS may have novel, noncatalytic biological functions. Our recent work shows that along with SUS, VDAC is also localized to the nucleus and these two proteins are inversely regulated in these two compartments under anoxic stress, indicating SUS-VDAC interaction may play a role in inter-compartmental signaling (Fig. 1).

Figure 1.

Current working model of SUS-VDAC interactions in maize root tip cells. Prolonged anoxia leads to de-oligomerization of VDAC and the release of SUS from mitochondria, resulting in the migration of SUS to the nucleus. We hypothesize that the nuclear accumulation of SUS signals the induction of cell death pathway leading to the death of the root tip in anoxic maize seedlings. The insets show the primary root tip and a part of the axis from aerobic and anoxic seedlings. The root tip death is indicated by Evans Blue staining pattern of the anoxic root. ≠ = SUS. □ = VDAC.

SUS mitochondrial localization also provided us an opportunity to reinterpret the phylogeny of sucrose metabolism. The proposed origin of sucrose metabolism is equivocal between the proteobacterial and cyanobacterial lineages.^9,10 Our discovery of SUS inside mitochondria, absence of plastid-bound SUS or plastid-targeting information in any of the plant SUS proteins and occurrence of mitochondrial targeting information in proteobacterial SUS orthologs strongly support a proteobacterial origin of plant sucrose synthases.⁸ Based on a genome-wide analysis of E. coli proteins, Lucattini et al.¹¹ proposed that mitochondrial targeting information may have been derived from the preexisting sequences of the endosymbiont proteins. We hypothesize that, in addition to the structural features needed for mitochondrial association, the functional basis of SUS-VDAC interaction may have been recruited by plants from the prokaryotic SUS genes. Based on striking similarities between bacterial and mitochondrial porins in their structure as well as regulation by purine nucleotides and their role in the host-cell death as modulated by cellular ATP levels, Frade and Michaelidis¹² speculated that the eukaryotic programmed cell death may have been a consequence of acquiring aerobic metabolism via the endosymbiotic process. Is organellar SUS a part of this acquisition?

Addendum to: Subbaiah CC, Palaniappan A, Duncan K, Rhoads DM, Huber SC, Sachs MM. Mitochondrial Localization and Putative Signaling Function of Maize Sucrose Synthase. J Biol Chem. 2006;281:15625–15635. doi: 10.1074/jbc.M600355200.