“…Recent investigators have implicated membrane composition and function [89,167,179,234], mitochondrial activity and number [97,179,[235][236][237], intracellular transport costs [130], DNA content [182,190], and other biochemical factors [238], as importantly involved in the intrinsic cellular control of metabolic scaling. Evidence for and against various specific aspects of this approach can be found in [19,20,89,[91][92][93][94]130,167,169,[235][236][237][238][239][240][241][242][243]. A major limitation of the cell-based RD approach is that it cannot explain by itself why the hypometric scaling of cellular metabolic rate is lost in cells cultured in vivo (reviewed in [20,97]).…”