Individual cristae within the same mitochondrion display different membrane potentials and are functionally independent
"The IMM consists of subcompartments called cristae and inner boundary membrane (IBM) (Palade, 1953). Cristae are invaginations protruding into the mitochondrial matrix, whereas the IBM runs parallel to the outer mitochondrial membrane (OMM). Cristae and IBM are connected via narrow tubular or slit‐like structures, known as crista junctions (CJs). In recent years, studies show that components of the electron transport chain (ETC) are confined to the lateral surfaces of the cristae rather than equally distributed along the IMM (Vogel et al, 2006; Wilkens et al, 2013). Moreover, dimers of F1F0 ATP Synthase assemble in rows along the edges of the cristae (Dudkina et al, 2005; Strauss et al, 2008; Davies et al, 2011). The CJs can be kept in a closed state by oligomers of the inner‐membrane dynamin‐like GTPase, OPA1 (Frezza et al, 2006; Pham et al, 2016), as well as components of the mitochondrial contact site and cristae organizing system (MICOS complex) (John et al, 2005; Rabl et al, 2009; Barrera et al, 2016; Glytsou et al, 2016)."
"Measurement of ΔΨm in individual cristae reveals that crista junctions provide electrical insulation and sustain polarization of individual mitochondrial cristae within a single mitochondrion even when neighbouring cristae are damaged.
Cristae have higher ΔΨ compared to their adjoining inner mitochondrial membranes.
Cristae are electrically insulated, allowing individual cristae within any given mitochondrion to have different membrane potentials.
Cristae can remain polarized despite depolarization of neighbouring ones.
Disruption of crista junctions impairs the electrical insulation of cristae, equilibrating their ΔΨ with those of inner mitochondrial membranes."
0e861268-7351-4a93-b006-63e94bc57d20-image.png
"This study raises interesting questions as to why mitochondria organize the ΔΨm in this way. One advantage, for example, could be related to the fact that ΔΨm constitutes the main energy available to drive protons through F1F0 ATP Synthase to produce ATP. As such, the localization of F1F0 ATP Synthase at the cristae rims appears to be advantageous in terms of proximity to the batteries. Another possible advantage could be compartmentalization of ΔΨm in each crista may serve as a safeguard mechanism restricting the impact of localized damage. In the case of the equipotential model, where the inner membrane of the entire mitochondrion represents a single capacitor, a breach in membrane integrity in one crista would cause a collapse in voltage in all cristae and compromise the function of the whole organelle. If, on the other hand, the IMM could maintain numerous, discrete electrochemical gradients, like a group of batteries, then failure of one or more would not invariably jeopardize the entire mitochondrion. This may be of particular relevance in cells harboring a highly interconnected mitochondrial network as opposed to cells with less elongated and/or branched mitochondria. Furthermore, the hetero‐potential model suggests that cristae with higher ΔΨCr‐IBM could compensate for cristae with impaired function."
532ae844-e9a1-4da1-812d-618037a326d3-image.png
"Hyperpolarized and depolarized IMM potentials are associated with different states of respiration. While both uncoupling and an increased rate of ATP synthesis dissipate ΔΨm, a decrease in ATP synthesis may result in hyperpolarization and increased ROS production. The hetero‐potential model of the mitochondrion allows for different cristae to serve different functions. In this model, some cristae could be more dedicated to ATP synthesis, whereas neighboring cristae could play a role in ROS signaling. The hetero‐potential model further allows for the consideration that different cristae may engage in primarily complex II vs. complex I respiration, which are associated with different membrane potentials and could be driven by different fuels."
Protonic Capacitor: Elucidating the biological significance of mitochondrial cristae formation
"[..]excess protons (positive charges) in an aqueous liquid on one side of a membrane will repel each other to become electrostatically localized along the membrane surface, attracting an equal number of excess hydroxyl anions (negative charges) to the other side of the membrane and thus resulting in a “protonic capacitor structure” (Fig. 2)."
0fe79372-d70c-496b-995f-8c2bcc327694-image.png
Consequences of Folding the Mitochondrial Inner Membrane
"The greater the energy requirements of a cell, the more inner membrane surface area it contains. Because there are practical limits to the volume fraction that cells can reserve for mitochondria, crista packing is maximized where energy demand is greatest, e.g., in cardiomyocytes the surface area of the inner membrane is more than tenfold that of the outer membrane."
"Although internalizing the chemiosmotic membrane is essential for mass production of ATP, it creates a complex and potentially risky situation for the cell. In particular, conditions that swell the matrix will cause the inner membrane to unfold and, eventually, rupture the outer membrane. In fact, cells use this demolition mechanism when death is the intended outcome. For example, inner membrane “herniation” of the outer membrane is observed in late stages of programmed cell death (extrinsic apoptosis) in FAS-activated liver (Figure 1). Crista contents, including cytochrome c, spill into the cytosol, resulting in irreversible loss of membrane potential and ATP production (Mootha et al., 2001). Matrix swelling in this case was attributed (Feldmann et al., 2000) to the mitochondrial permeability transition pore, MPTP, the opening of which can drive an osmotic influx of water sufficient to unfold the inner membrane and rupture the outer membrane (e.g., Rasola and Bernardi, 2011)."
"Extreme crista swelling is as perilous to the cell as uncontrolled matrix swelling, e.g., the total volume of a few fully expanded cristae in a single muscle mitochondrion easily exceeds the volume enclosed by the outer membrane. In fact, rupture of the outer membrane by crista (not matrix) swelling occurs in insect flight muscle as a prelude to apoptosis (Walker and Benzer, 2004). Clearly, the process of unfolding the inner membrane is as important to cell survival as generating the crista folds and likely is regulated as carefully."
"Although, at first glance, it seems risky to fold a large membrane within an outer membrane, rupture of which is fatal, this situation actually provides the cell an advantage. When mitochondria are suspended in hypo-osmotic media, outer membranes lyse at sucrose gradients tenfold greater than liposomes or mitochondrial inner membrane vesicles of similar size, typically 20–30 mM (Douce et al., 1972; Li et al., 1986). This dramatic protection against osmotic stress directly accrues from the outer membrane being osmotically inactive, i.e., very permeable to small solutes. The chemiosmotic inner membrane is the mitochondrial osmometer. Swelling of the matrix caused by osmotic influx of water compresses the cristae before significant pressure is applied to the outer membrane by outward expansion of the inner membrane. In effect, unfolding the inner membrane absorbs significant osmotic stress and delays irreversible damage to the mitochondria. Equally important, this indirect rupture mechanism provides the cell the opportunity to regulate outer membrane lysis."
"A mechanism has been proposed that would protect mitochondria against outer membrane lysis and inner-membrane domain mixing during crista swelling: fusion of tubular cristae to form larger cristae more adaptable to volume changes. Crista fusion was suggested by the first EM tomograms of mammalian mitochondria, which revealed complex cristae with tubular and lamellar regions (Mannella et al., 1997; Perkins et al., 1997). Larger cristae are more prevalent in condensed mitochondria; decreased matrix volume brings cristae into closer proximity, favoring fusion (Mannella et al., 2001). It is likely that crista fusion in response to matrix contraction is quite extensive. Condensed liver mitochondria have large dilated cristae with multiple (up to seven) junctions (Mannella et al., 1997) and condensed yeast mitochondria may have a single dilated internal cavity with much of the inner membrane pulled away from the outer membrane and no well-defined crista junctions or cristae (Mannella et al., 2001)."
