UCP1 - A sophisticated energy valve.

This review focuses on the biochemical work of UCP1 starting from the early observation by Ricquier and Kader in 1976. We entered this field in 1980 with the isolation of native UCP1 and then reported the amino acid sequence structure discovering a strong homology to the ADP/ATP carrier. With the isolated native UCP1 we studied structural and functional features, in particular the complex characteristics of nucleotide binding.

Dataset of the AAC2 conformations in the c-, intermediate- and m-states obtained from free-energy simulations.

The data reported herein are related to the article entitled: "The switching mechanism of the mitochondrial ADP/ATP carrier explored by free-energy landscapes" (Pietropaolo et al., 2016) [1]. We report the coordinates of the ADP/ATP carrier (AAC2) in the presence and absence of adenine and guanine nucleotides in the c-, intermediate- and m-states obtained from the free-energy simulations and corresponding to the free-energy minima.

The switching mechanism of the mitochondrial ADP/ATP carrier explored by free-energy landscapes.

The ADP/ATP carrier (AAC) of mitochondria has been an early example for elucidating the transport mechanism alternating between the external (c-) and internal (m-) states (M. Klingenberg, Biochim. Biophys.

Wanderings in bioenergetics and biomembranes.

Having worked for 55 years in the center and at the fringe of bioenergetics, my major research stations are reviewed in the following wanderings: from microsomes to mitochondria, from NAD to CoQ, from reversed electron transport to reversed oxidative phosphorylation, from mitochondrial hydrogen transfer to phosphate transfer pathways, from endogenous nucleotides to mitochondrial compartmentation, from transport to mechanism, from carrier to structure, from coupling by AAC to uncoupling by UCP, and from specific to general transport laws. These wanderings are recalled with varying emphasis paid to the covered science stations.

Cardiolipin and mitochondrial carriers.

Members of the mitochondrial carrier family interact with cardiolipin (CL) as evident from a variety of functional and structural effects. CL stabilises carrier proteins on isolation with detergents, with the P(i) carrier as the prime example. CL is required for transport in reconstituted vesicles, prime examples are the P(i)- and ADP/ATP carrier (AAC).

The ADP and ATP transport in mitochondria and its carrier.

Different from some more specialised short reviews, here a general although not encyclopaedic survey of the function, metabolic role, structure and mechanism of the ADP/ATP transport in mitochondria is presented. The obvious need for an "old fashioned" review comes from the gateway role in metabolism of the ATP transfer to the cytosol from mitochondria. Amidst the labours, 40 or more years ago, of unravelling the role of mitochondrial compartments and of the two membranes, the sequence of steps of how ATP arrives in the cytosol became a major issue.

Transport viewed as a catalytic process.

Transport catalysis is analysed in terms of the "induced transition fit" (ITF) concept. The essentials of ITF are briefly elucidated, emphasizing the difference of substrate-protein interactions between enzymes and carriers exemplified by the paradigm ADP/ATP carrier (AAC). Two of the numerous applications of the ITF are discussed in more detail: unidirectional passive and active transport and the relation of substrate site type inhibitors to the carrier conformations.

Transport catalysis.

Carrier linked solute transport through biomembranes is analysed with the viewpoint of catalysis. Different from enzymes, in carriers the unchanged substrate induces optimum fit in the transition state. The enhanced intrinsic binding energy pays for the energy required of the global conformation changes, thus decreasing the activation energy barrier.

When a common problem meets an ingenious mind.

The invention of the modern micropipette

Ligand-protein interaction in biomembrane carriers. The induced transition fit of transport catalysis.

Carrier-linked transport through biomembranes is treated under the view of catalysis. As in enzymes, substrate-protein interaction yields catalytic energy in overcoming the activation barrier. At variance with enzymes, catalytic energy is concentrated on structural changes of the carrier rather than on the substrate destabilization for facilitating the global protein rearrangements during transport.

A large Ca2+-dependent channel formed by recombinant ADP/ATP carrier from Neurospora crassa resembles the mitochondrial permeability transition pore.

Strong support for the central role of the ADP/ATP carrier (AAC) in the mitochondrial permeability transition (mPT) is provided by the single-channel current measurements in patch-clamp experiments with the isolated reconstituted AAC. In previous work [Brustovetsky, N., and Klingenberg, M.