Mitochondrial Respiration

Cellular oxygen (O2) consumption and carbon dioxide (CO2) production (respiration) occurs within specialized sub-cellular organelles called mitochondria. Parts of a mitochondrion are shown on the left, where you can see two outer membranes, and where the inner membrane invaginates internally to form long strands (cristae) that extend into the inner regions of the organelle. These cristae also increase the volume of the space or compartment between the two mitochondrial membranes, termed the inter-membranous space. As you are learning, the multiple metabolic pathways do not exist is isolation from each other, and to fully grasp the purpose of cellular respiration you need to understand its place in the cascade of pathways that exist to regenerate cellular ATP.  For example, mitochondria need substrates to fuel their pathways, and some of these are the end products of prior pathways involved in glucose oxidation (glycolysis) and amino acid oxidation, and others such as inorganic phosphate are derived from ATP hydrolysis within the cytosolic phosphagen system.  As these substrates are available, with the obvious important one being O2, mitochondria covert pyruvate to acetyl CoA, NADH and a CO2, and sequentially degrade acetyl CoA, which also is produced from the B-oxidation of fatty acids, to fuel the tricarboxylic acid (TCA) cycle. Here added CO2 is produced and added electrons and protons (H+) are removed and captured in the formation of more NADH and FADH2.  These electron carriers then release their electrons and H+ loads to the electron transport chain located along the inner mitochondrial membrane. You will learn of the components of the electron transport chain, why their is stoichiometry between electron transport and H+ translocation to the inter-membranous space, and how this explains the accepted ATP equivalents for NADH and FADH2 being 3 and 2, respectively. Of added importance is the barriers imposed by the mitochondrial membranes (mainly the outer membrane).  How do certain molecules get it, and how does the ATP get out? What biochemical events dictate the predominance of fat, carbohydrate or amino acids as the fuel for energy catabolism? What determines how many mitochondria exist within a given skeletal muscle fibre? All of these questions are important, and all have answers that you are capable of understanding after your study of this material.

Recommended sequence of topics:


Pyruvate oxidation

The TCA cycle

Summary of the TCA cycle

Mitochondrial shuttles and transporters

Electron transport chain

Oxidative phosphorylation


Carnitine shuttle

Fatty acid oxidation

Comparing CHO vs. fat oxidation

Amino acid oxidation