chapter  9
52 Pages

Drugs, Nutrients, and Hormones in Mitochondrial Function

Introduction .......................................................................... 456 Compounds Generating Free Radicals ............................... 457

Vacor ........................................................................... 458 Streptozotocin .............................................................. 459 Alloxan ......................................................................... 460

Pharmaceuticals ................................................................... 461 Zidovudine.................................................................... 461 OXPHOS Stimulants/Inhibitors................................. 462

Drugs..................................................................................... 463 Adriamycin................................................................... 463 Hypoglycemic Agents .................................................. 464 NSAID .......................................................................... 466 Ethanol......................................................................... 466 Statins .......................................................................... 467

Hormones.............................................................................. 468 Thyroid Hormone ........................................................ 468 Nutrients...................................................................... 471 Exercise ........................................................................ 471 Other Hormones .......................................................... 471 Miscellaneous Compounds.......................................... 472

Hormones and Nutrients in Mitochondrial Gene Expression.......................................................... 472 Growth (Factors That Stimulate Growth)................. 473 Exercise ........................................................................ 474

Hormones.............................................................................. 475 Thyroid Hormone ........................................................ 475 Glucocorticoids............................................................. 477 Insulin .......................................................................... 478

Nutrients............................................................................... 478 Vitamin A (Retinoic Acid) ........................................... 478 Vitamin D .................................................................... 480 Vitamin B12................................................................. 481 Iron ............................................................................... 481 Peroxisomal Proliferators ........................................... 481

References............................................................................. 484

INTRODUCTION

Mitochondria (mt) have long been known to be sensitive to a wide variety of compounds that include drugs, nutrients, and hormones. Among the first to be reported are those that influence the respiratory chain and the coupling of respiration to ATP synthesis (oxidative phosphorylation, OXPHOS). These compounds (see Table 1.7, Chapter 1) allowed scientists to learn how the chain worked and how its function was linked to that of ATP synthesis. Of course, some of these compounds were not drugs for the treatment of disease but merely tools of the biochemist. Yet, their use paved the way for subsequent investigations with compounds that had a direct effect on mt OXPHOS or an indirect effect via changes in mt gene expression, changes in mt membrane function, or induction of free radical damage to the genome or the membranes. In addition,

many compounds affect mt function secondarily; this effect developed unintentionally and was not the primary purpose of the drug.