Although the overall processes of photosynthesis and mitochondrial oxidation are well understood, many important details remain to be uncovered. For example, while increasingly high-resolution structures of complexes and supercomplexes are being determined, many of the mechanistic details underlying the function and regulation of electron-transport chains and their associated reactions (proton translocation, oxygen generation, etc.) remain to be established. Moving beyond this static picture of these remarkably complex structures requires additional biophysical analysis of the dynamics underlying their activities. For example, we do not know with certainty the pathway taken by protons during proton pumping in some of the electron-transport complexes.

Although the binding-change mechanism for ATP synthesis by the F₀F₁ complex is now generally accepted, we do not understand precisely how conformational changes in each β subunit are coupled to the cyclical binding of ADP and P_i, formation of ATP, and then release of ATP. In addition, many questions remain about the precise mechanism of action of the transport proteins in the inner mitochondrial and chloroplast membranes that play key roles in oxidative phosphorylation and photosynthesis.

We now know that the release of cytochrome c and other proteins from the intermembrane space of mitochondria into the cytosol plays a major role in triggering apoptosis (see Chapter 21). Certain members of the Bcl-2 family of apoptotic proteins as well as ion channels localized in part to the outer mitochondrial membrane participate in this process. The connections between energy metabolism and mechanisms underlying apoptosis remain to be clearly defined, as does the channel, called the mitochondrial permeability transition pore (mPTP), that is responsible for the permeabilization of the inner membrane to small molecules.

The recognition over the past decade of the importance of mitochondrial dynamics (e.g., fusion and fission) to mitochondrial function has set the stage for detailed molecular genetic analysis of these processes. Several of the key players in fusion and fission have been identified, but many additional components and their mechanisms of action have yet to be discovered, such as those involved in the coordinated fusion of inner membranes with each other and outer membranes with each other.

The role of reactive oxygen species (ROS) in cell biology is an active area of research. ROS-mediated cellular stress is now thought to play a role in many diseases and will probably continue to be a major area of research in the coming years. In addition to their role in cellular oxidative stress, ROS can serve as signaling molecules that alter nuclear gene expression, a process sometimes called retrograde signaling. It appears that ROS and other small molecules released from the mitochondrion and chloroplast can be used to inform the nucleus about the metabolic status of each organelle and thus permit appropriate regulation of gene expression in response. In some cases, this regulation involves compensatory activation of protective genes. In others, it may involve increasing or decreasing the production of nuclear-encoded proteins to insure proper organelle functioning. The mechanisms of these signaling pathways, which in some cases involve redox reactions with thiols on signaling molecules, are actively being investigated.

The discovery of tunneling nanotubes and the intercellular movement of mitochondria is an unexpected and exciting development. The general significance and in vivo function of both of these phenomena remain to be established. Continued characterization of another relatively recent discovery, beige-fat cells, holds out the prospect of a much deeper understanding of energy metabolism and the possibility of new approaches to manipulate this metabolism to promote health and prevent or treat disease.

As we better understand the mechanisms underlying photosynthesis, particularly the action of rubisco—both its regulation and its influence on photosynthesis and overall chloroplast metabolism—it is possible that we will be able to exploit these insights to improve crop yields to provide abundant and inexpensive food to all who need it.