FUNCTIONAL CHANGES IN STRUCTURE 8 1 



strates are required only to iniliale or sparkle the oxidation oi fatly acids (15). it is 

 unlikely that lipid is synthesized //; sitti in starving cells. The lipid inclusions found in 

 this situation in certain cells (e.g., the muscle fibers of the myocardiinn and the exocrine 

 cells of the pancreas) are prolialily derived from the mobilized fat of the adipose tissue 

 of the animal. Therefore, their intracellular accumulation should he interpreted in terms 

 of the relationship between the rate of local lipid oxidation and the rate of lipid trans- 

 port from the fat depots of the body to the recipient cell. 



Dr. Spirtes: How tlo the follow ing fads Ht in w ilb your theory of function of mito- 

 chondria around lipid droplets after 4S hours star\ation.' /) fatty acid oxidation little 

 decreased; and 2) fatty acid synthesis extremely low ? 



Dr. P.\L.\nE: They fit in very v\'ell, since I believe that the lipid inclusions found in the 

 starving cells are not made up of newly synthesized lipid. They represent mobilized 

 fat, brought in from the depots of the organism, to be oxidized by the mitochondria of 

 the myocardium or the pancreas. 



Dr. Weber: I shoukl like to ask Dr. Palade a question concerning the striking asso- 

 tion of mitochondria and lipoid droplets. Is this an indication that mitochondria take 

 part in the elaboration of lipoid droplets — as it has been assumed in studies from light 

 microscopy — or is this only a transitional association, needed for a certain functional 

 period ? 



Dr. Pal.\de: As indicated by Dr. Weber, it has been repeatedly postulated — on the 

 basis of light microscope observations — that mitochondria are involved in the formation 

 of lipid inclusions, the prevalent assumption being that the organelles are bodily trans- 

 formed into lipid masses (cf. 35, 22). Our experiments on starved animals indicate that 

 the association is transitory and should be considered as an expression of fat removal 

 by oxidation, rather than of fat synthesis. Preliminary observations show that a similar 

 mitochondrion-lipid association is encountered in the glycogen-loaded liver of cortisone- 

 treated rats. In this condition, lipid is probably synthesized from surplus carbohydrate. 

 In both cases, however, the association should be interpreted in terms of close apposition 

 of a tool (the mitochondrial enzymes involved in lipid metabolism) to either raw 

 material (lipid to be oxidized), or product (synthesized lipid). In the light microscope 

 literature, the mitochondrion was usually considered as raw material on its way to be 

 converted into a lipid inclusion. With our present knowledge of mitochondrial chem- 

 istry and enzymology. this type of relationship appears very unlikely, at least under 

 normal conditions. 



Dr. Novikoff: I v/ould like to ask two questions: /) Has Dr. Palade studied path- 

 ological material? For example, at the edge of a myocardial infarct lipid droplets 

 accumulate in perfectly linear fashion, just like the mitochondria which apparently dis- 

 appear. This might be good material in which to examine the old notion concerning 

 mitochondrial degeneration into lipid droplets. 2) Dr. Palade speaks of two outer mito- 

 chondrial membranes. Would it not be preferable to speak of one external membrane 

 enclosing the mitochondrial body? The latter has 'cristae' and, of course, an outer limit. 

 This outer limit apparently remains cjuite \isible e\cn though the external membrane 

 cannot be resolved at the time mitochondrion and lipid droplet are in close association. 

 As Dr. Palade has indicated, it is likely that the enzymes of oxidative phosphorylation 

 are in the mitochondrial body, but not, as suggested by work from Dr. Green's lab- 

 oratory, in the external membrane. 



