Paracellular transport as a strategy for energy conservation by multicellular organisms?

Abstract

Paracellular transport of solutes and water accompanies transcellular transport across epithelial barriers and together they serve to maintain internal body composition. However, whether paracellular transport is necessary and why it evolved is unknown. In this commentary I discuss our recent studies to address this question in the proximal tubule of the kidney. Paracellular reabsorption of sodium occurs in the proximal tubule and is mediated by claudin-2. However, deletion of claudin-2 in mice does not affect whole kidney sodium excretion because it can be completely compensated by downtream transcellular transport mechanisms. This occurs at the expense of increased oxygen consumption, tissue hypoxia and increased susceptibility to ischemic injury. It is concluded that paracellular transport acts as an energy saving mechanism to increase transport without consuming additional oxygen. It is speculated that this might be why paracellular transport evolved in leaky epithelia with high transport needs.

Keywords: oxygen; paracellular; tight junction; transport.

Figure 1.

Function of the renal tubule. (A) Filtration of blood through the glomerulus. Filtrate composition is identical to plasma. (B) Bulk transport in the proximal tubule. Transepithelial flux of solutes and water is high. Tubule fluid composition is moderately different from plasma and transepithelial gradients are just beginning to be established. (C) Fine-tuning in the distal tubule. Transepithelial transport capacity is low but largely driven uphill against steep and thermodynamically unfavorable transepithelial gradients, thereby requiring considerable energy consumption for active transport.

Figure 2.

Role of claudin-2 in renal O₂ utilization. (A) Relationship between T_Na and QO₂ in individual claudin-2 wild-type (WT) and knockout (KO) mice, expressed per gram of kidney weight (kwt). (B) Efficiency of O₂ utilization for renal Na⁺ transport, T_Na/QO₂, calculated from the data in A (n = 7 per group). *P < 0.01, by Student's t test. Reproduced with permission from Pei L. et al., Paracellular epithelial sodium transport maximizes energy efficiency in the kidney. J Clin Invest, 126: 2509–2518, 2016.

Figure 3.

Analogous energy-saving strategies in biology and automotive engineering. (A) Hybrid car. Gasoline provides the fuel for a gasoline engine that provides the primary source of propulsion. Regenerative braking uses kinetic energy to recharge a battery, thereby driving additional propulsion via an electric motor. (B) Transporting epithelium. ATP provides the energy for transcellular transport driven by a membrane ATPase. Electrochemical gradients generated by transcellular transport constitute a store of potential energy available to drive additional passive transport via paracellular diffusion.