Regulation of Organelle Acidity

• DOI: 10.1085/jgp.117.4.329
• Publication Date: 2002-07-26T16:50:20Z
• Authors: Michael Grabe; George Oster
• Keywords: Organelle; Proton Transport; Antiporters; Proton Pump

Intracellular organelles have characteristic pH ranges that are set and maintained by a balance between ion pumps, leaks, internal ionic equilibria. Previously, thermodynamic study Rybak et al. (Rybak, S., F. Lanni, R. Murphy. 1997. Biophys. J. 73:674–687) identified the key elements involved in regulation; however, recent experiments show cellular compartments not equilibrium. We present here nonequilibrium model of lumenal acidification based on interplay pumps channels, physical properties matrix, organelle geometry. The successfully predicts experimentally measured steady-state transient values membrane potentials. conclude morphological differences among insufficient to explain wide range pHs cell. Using sensitivity analysis, we quantified influence regulatory dynamics acidification. found V-ATPase proton pump leak densities two parameters most strongly resting pH. Additionally, modeled response Golgi complex varying external solutions, our findings suggest is permeable more than one dominant counter ion. From this data, determined permeability 8.1 × 10−6 cm/s. Furthermore, analyzed early-to-late transition endosomal pathway where Na,K-ATPases been shown limit an entire unit. Our supports role Na,K-ATPase regulating affecting potential. However, experimental data can only be reproduced (1) positing existence hypothetical voltage-gated chloride channel or (2) newly formed vesicles especially high potassium concentrations small conductance.