Desmin Interacts Directly with Mitochondria

Alexander A Dayal,Natalia V Medvedeva,Tatiana M Nekrasova,Sergey D Duhalin,Alexander A Minin,Alexey K Surin

doi:10.3390/ijms21218122

Abstract

Desmin intermediate filaments (IFs) play an important role in maintaining the structural and functional integrity of muscle cells. They connect contractile myofibrils to plasma membrane, nuclei, and mitochondria. Disturbance of their network due to desmin mutations or deficiency leads to an infringement of myofibril organization and to a deterioration of mitochondrial distribution, morphology, and functions. The nature of the interaction of desmin IFs with mitochondria is not clear. To elucidate the possibility that desmin can directly bind to mitochondria, we have undertaken the study of their interaction in vitro. Using desmin mutant Des(Y122L) that forms unit-length filaments (ULFs) but is incapable of forming long filaments and, therefore, could be effectively separated from mitochondria by centrifugation through sucrose gradient, we probed the interaction of recombinant human desmin with mitochondria isolated from rat liver. Our data show that desmin can directly bind to mitochondria, and this binding depends on its N-terminal domain. We have found that mitochondrial cysteine protease can disrupt this interaction by cleavage of desmin at its N-terminus.

Highlights

Intermediate filament (IF) networks are one of three cytoskeletal components along with microtubules and actin microfilaments
To predict the presence of mitochondrial in the molecule of human flanked by two groups of positively charged amino acids—a characteristic pattern of many proteins desmin, we used the online program TargetP 1.1 [15] to analyze its sequence and found that such knownisto be localized to outer mitochondrial membrane (OMM)
Our results show that pure recombinant Des(Y122L) can bind to isolated rat liver mitochondria without intermediary

Summary

Introduction

Intermediate filament (IF) networks are one of three cytoskeletal components along with microtubules and actin microfilaments. A major constituent of the IF network inside muscle cells, is a good example of such factors controlling mitochondria. A plethora of pathological conditions, collectively known as desminopathies, is caused by mutations in desmin and results in abnormalities in mitochondrial distribution and morphology as well as reduced mitochondrial respiratory function [5,7,8,9]. These data suggest that interaction with desmin is a prerequisite for normal mitochondrial functioning.

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Conclusion