Although mitochondria (MI) are intensively studied cell organelles [1][2][3][4] and even the redox communication with electrodes has been addressed, [5] there is still a demand for techniques to probe their properties under (patho-)physiological conditions. The integrity of the mitochondrial membrane and changes in its composition play a crucial role in preventing or even triggering apoptosis. Here, we report that isolated functionally intact MI interact with the surface of a static mercury electrode in a way which is similar to the adhesion-spreading of liposomes [6][7][8][9] and thrombocytes, [10] that is, they attach to the hydrophobic mercury surface and disintegrate by forming islands of adsorbed molecules. This attachment is caused by the hydrophobic interaction between mercury and the lipid chains, [11] a topic with a long history and recently reviewed by Nelson.[12] This attachment is measurable because of the changes of double-layer capacity, which give rise to defined capacitive signals. The quantitative analysis of these signals allows the determination of the phase-transition temperature of the mitochondrial membrane, the determination of the size of MI, and indicates the physiological status of MI.Freshly isolated MI dispersed in a physiological KCl solution interact with the Hg surface giving capacitive current spikes which have a positive sign at negative potentials (Figure 1), and a negative sign at positive potentials versus the point of zero charge (pzc). The highest frequency of spikes was observed at À0.9 V. This is very similar to the behavior of lecithin liposomes, indicating that the mitochondrial membrane also disintegrates on Hg and forms an island of adsorbed molecules. Counting the number of current spikes per time and surface area units allows analysis of the macrokinetics, that is, the number of disintegrations as a measure of the rate at which the MI interact with the Hg surface.For each MI we can also analyze the microkinetics, that is, the rate at which a single MI disintegrates. This can be accessed through integration of the single current spikes to yield charge (Q)-time (t) traces, which mirror the timeresolved disintegration, leading to the displacement of the aqueous side of the electric double layer of the Hg electrode by the adsorbed constituents of the mitochondrial membrane (including cardiolipins; Figure 2). The resulting charge-time trace follows the same equation [Eq. (1)] as the traces reported for liposomes, [6][7][8][9]13] where t 1 and t 2 are two time constants, characterizing the rate of adhesion and spreading, respectively, and Q 0 , Q 1 , and Q 2 are constants. Figure 3 shows typical and reproducible Arrhenius plots of the macrokinetics (J is the peak frequency per unit area) for MI isolated from BRIN-BD11 cells grown under two different conditions, that is, normoglycemic (5.5 mmol L À1 glucose) and hyperglycemic (25 mmol L À1 glucose) conditions. There is a pronounced break of the straight lines at around 27.5 8C. This break is typical for a phase transition, a...