Mitochondria are the cells' powerhouse that produce the ubiquitous energy currency (ATP) by consuming oxygen, producing water and building up the proton motive force. Oxygen consumption is a classical means of assessing energy expenditure, one component of energy balance. When energy balance is positive, weight increases. This is observed during the dynamic phase of obesity, and during body composition changes associated with aging. Whether intrinsic defaults in mitochondria occur is the matter of this review. Indeed, the ratio of ATP over oxygen consumed, which is not fixed, is one way of regulating heat release and ATP flux, but can also be the consequence of environmental conditions of mitochondrial work. For example, various hormones (T3, glucocorticoids), changes in lipid membrane composition, changes in food intake and exercise, and various drugs, can modify the ratio of ATP over oxygen consumed. Aging and insulin resistance are other regulators of this ratio. Finally there is a rising body of evidence linking diabetes to mitochondrial functions.