Human epidermal energy metabolism is functionally anaerobic

We have reported that epidermal Langerhans cells possess an H(+)-extruding mechanism signalling their existence in an anaerobic environment. This study highlights the energy metabolism of human epidermis. In their habitual state the keratinocytes contain more lactate than do most other cell types. Their lactate production in vitro is vigorous and independent of oxygen and most of it is released to the medium. Autoincubation of the epidermis under starved conditions resulted in a 30% increase of lactate, indicating ongoing glycogenolysis. Iodoacetate inhibited lactate production by > 90%. Energy charge values were low, approximately 0.82, and comparable with those previously reported for smooth muscle. Moreover, the overwhelming majority of the keratinocytic mitochondria had an appearance markedly deviating from those in the Langerhans cells, melanocytes and fibroblasts, and, above all, were characterized by an enormous reduction of the inner membrane. This structure is in all probability incompatible with an effective oxidative metabolism of glucose. We conclude that epidermal energy metabolism is predominantly anaerobic in spite of the formal presence of mitochondria. The high production of lactate obviously demands extracellular transport pathways for rapid elimination of this organic acid. An extracellular space complying with such a demand emerges on electron microscopy when an isotonic glutaraldehyde-based fixative is used. The prevailing view regarding the size of the extracellular space is based on the common use of hypotonic fixatives, such as Karnovski's fixative, which causes gross cellular swelling and concomitant near total elimination of the extracellular space, leaving interstices with a diameter significantly smaller than that allowing fluid flow.