Cost, effectiveness and environmental relevance of multidrug transporters in sea urchin embryos

Abstract

SUMMARY ATP-binding cassette transporters protect cells via efflux of xenobiotics and endogenous byproducts of detoxification. While the cost of this ATP-dependent extrusion is known at the molecular level, i.e. the ATP used for each efflux event, the overall cost to a cell or organism of operating this defense is unclear, especially as the cost of efflux changes depending on environmental conditions. During prolonged exposure to xenobiotics, multidrug transporter activity could be costly and ineffective because effluxed substrate molecules are not modified in the process and could thus undergo repeated cycles of efflux and re-entry. Here we use embryos of the purple sea urchin, Strongylocentrotus purpuratus, as a model to determine transport costs and benefits under environmentally relevant xenobiotic concentrations. Strikingly, our results show that efflux transporter activity costs less than 0.2% of total ATP usage, as a proportion of oxygen consumption. The benefits of transport, defined as the reduction in substrate accumulation due to transporter activity, depended largely, but not entirely, on the rate of passive flux of each substrate across the plasma membrane. One of the substrates tested exhibited rapid membrane permeation coupled with high rates of efflux, thus inducing rapid and futile cycles of efflux followed by re-entry of the substrate. This combination significantly reduced transporter effectiveness as a defense and increased costs even at relatively low substrate concentrations. Despite these effects with certain substrates, our results show that efflux transporters are a remarkably effective and low-cost first line of defense against exposure to environmentally relevant concentrations of xenobiotics.

Experimental ocean acidification alters the allocation of metabolic energy

“…This ∼30% difference in the allocation of metabolic energy could reduce an organism's ability to respond to additional energy-demanding environmental stressors and has more general implications for the ability to sustain fundamental biochemical processes (23). For instance, even a relatively small energy requirement for responses to environmental toxicants (24) and other macromolecular synthesis requirements [e.g., RNA (25)] could be constrained by changes in ATP allocation. A comprehensive accounting of the variations in each of the major processes supported by total ATP would improve predictions from models attempting to understand biological responses to ocean acidification and other compounding environmental stressors.…”

The Sea Urchin Embryo: A Model for Studying Molecular Mechanisms Involved in Human Diseases and for Testing Bioactive Compounds

“…Members of the ATP-binding cassette (ABC) superfamily transport-specific molecules and substrates across membranes and mutations in these genes contribute to several human genetic disorders [90]. In sea urchin embryos, efflux transporter genes act as a first line of defense against toxic xenobiotic compounds; their expression is upregulated after fertilization [91], and this process is accomplished with relatively small energy costs [92,93]. Cytochrome P450 family (CYPs) enzymes catalyze the oxidation of many xenobiotics, environmental chemicals, and drugs and protect the embryo from toxicants.…”

Fluid flow enhances the effectiveness of toxin export by aquatic microorganisms: A first-passage perspective on microvilli and the concentration boundary layer

“…Toxin molecules released at the tips of microvilli will be advected away from the embryo, decreasing the probability that they will be reabsorbed and have to be exported again, which is energentically costly for the embryo. Within the biological transporter literature, this sequence of export and subsequent reabsorption is refered to as futile cycling [22].…”