Ultrastructural Bases for Metabolically Linked Mechanical Activity in Mitochondria

Abstract

Isolated mitochondria are capable of undergoing dramatic reversible ultrastructural transformations between a condensed and an orthodox conformation. These two conformations are the extremes in ultrastructural organization between which structually and functionally intact mitochondria transform during reversible respiratory cycles. It has been found that electron transport is required for the condensed-to-orthodox ultrastructural transformation which occurs in mitochondria under State IV conditions, i.e., under conditions in which exogenous substrate is present and ADP is deficient. Inhibition of State IV electron transport at the cyanide-, antimycin A-, or Amytal-sensitive sites in the respiratory chain results in inhibition of this transformation. Resumption of electron transport in initially inhibited mitochondrial systems, initiated by channeling electrons through pathways which bypass the inhibited sites, results in resumption of the ultrastructural transformation. The condensed-toorthodox transformation is DNP insensitive and, therefore, does not require participation of the coupling enzymes of the energy-transfer pathway. It is concluded that this ultrastructural transformation is manifest by the conversion of the chemical energy of electron transport directly into mechanical work. The reversed ultrastructural transformation, i.e., orthodoxto-condensed, which occurs during ADP-activated State III electron transport, is inhibited by DNP and parallels suppression of acceptor control and oxidative phosphorylation. Mechanochemical ultrastructural transformation as a basis for energy transfer in mitochondria is considered with respect to the results presented.

Dynamics, structure, and function are coupled in the mitochondrial matrix.

“…(B) Mitochondria from the sample at 300 mOsm were in the condensed configuration: the matrix is decreased in size (matrix protein concentration, 560 mg/ml) and there is a large intermembrane space. Mitochondrial configuration is also dependent on respiratory state (5,6). In 300 mOsm medium, state IV (respiratory substrate and 02) mitochondria are orthodox, state III (respiratory substrate and 02 and ADP) mitochondria are fairly condensed, and state IV(i) (respiratory substrate and 02 and respiratory inhibitor) mitochondria are very condensed (see text for the functional definitions of these states).…”

“…1) (5,6). In rat liver, the matrix of the condensed mitochondrion occupies about 50%o of the total mitochondrial volume and contains about 56% (wt/vol) protein, whereas the matrix of the orthodox mitochondrion occupies nearly the entire mitochondrial volume and contains about 26% protein (7).…”

“…In rat liver, the matrix of the condensed mitochondrion occupies about 50%o of the total mitochondrial volume and contains about 56% (wt/vol) protein, whereas the matrix of the orthodox mitochondrion occupies nearly the entire mitochondrial volume and contains about 26% protein (7). These mitochondrial configurations are dependent on the osmolarity of the external medium and on respiratory state-i.e., whether or not the mitochondria are active in electron transport and ATP synthesis (5,6,8).…”

Energy-Linked Ultrastructural Transformations in Isolated Liver Mitochondria and Mitoplasts

“…Identical energy-linked ultrastructural transformations occur in mitochondria within the intact cell when oxidative phosphorylation is induced (4) . Although there is currently no general agreement as to a basic mechanism by which energy metabolism is coupled to ultrastructural trans-formations in mitochondria (5), there is considerable evidence that such transformations occur during steady state as well as oscillatory state electron transport and during oxidative phosphorylation (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) .…”

“…These transformations are known to be reversible (I), are energy dependent (2), and occur under conditions which are favorable for maintaining the integrity of oxidative phosphorylation (2, 3) . Identical energy-linked ultrastructural transformations occur in mitochondria within the intact cell when oxidative phosphorylation is induced (4) .…”