The conventional MMP-sensitive probes provide information regarding Δ Ψ. But however this is only partial information. In fact, in some cases changes in Δ Ψ may be counterbalanced (to different degrees) by ΔpH changing in an opposite direction to partially restore the true electrochemical driving force for ATP production, ΔpH (reviewed in ) (Santo-Domingo and Demaurex 2012)). Therefore, measuring mitochondrial pH is required for a complete measurement of the electrochemical gradient, the driving force for ATP production and IMM driven thermogenesis . Measuring mitochondrial pH also can provide new and unexpected insights into mitochondrial function, state and even mitochondrial stress/dysfunction seen in many diseases. The significance of mitochondrial pH is often overlooked, however it is crucial in many physiologically relevant processes such as insulin secretion , calcium homeostasis (Poburko, Santo-Domingo, and Demaurex 2011), and apoptosis . Generally, mitochondrial matrix is more basic (pH ~7.8-8) than intermembrane space which is similar to cytosol (pH ~ 7) as a result of the ETC-driven proton pumping. However, mitochondrial matrix alkalinisation is considered an early signal of apoptotic mitochondria with concomitant cytosolic acidification . Additionally, proton movement through the nearly impermeable inner membrane of mitochondria is intrinsically coupled with the influx-efflux of ions to maintain osmotic balance . Volume homeostasis of mitochondria is very crucial for the overall functioning of mitochondria.