Mitochondrial vulnerability to aldehydic load and the role mitochondrial aldehyde dehydrogenases.

Mitochondria are the metabolic hubs of the cell; they are major sites of ATP production through cellular respiration and the electron transfer chain, and thus generators of certain amounts of reactive oxygen species (ROS); they participate in the production of most of the cell building blocks, including nucleotides and amino acids; they produce many hormones and neurotransmitters; and they have extensive metabolic reactions, including carbohydrate and lipids metabolism. All these mitochondrial activities contribute to accumulation of toxic and reactive aldehydes that can react with all macromolecules. Accumulated aldehydes covalently bind to proteins, DNA, and lipids, damaging these macromolecules and thus the mitochondrial functions. It is therefore not surprising that mitochondrial dysfunction is associated with many acute and chronic human diseases. In addition to endogenous biogenic aldehydes, exogenous aldehydes, such as those from air pollution, highly processed or fried food, can contribute to mitochondrial dysfunctions through increased mitochondrial aldehydic load. Here we discuss some of the built-in mechanisms in mitochondria that help detoxify aldehydes; these are members of a larger family of aldehyde dehydrogenases (ALDHs) that provide some defense from aldehydic load. Aldehydic burden on the mitochondria can also be reduced through simple lifestyle changes. Although such changes alone are insufficient, increasing public health awareness may provide a path for a more effective action to reduce the contribution of mitochondrial dysfunction to human pathologies. (228/250 words)