Abstract

Cristae architecture is important for the function of mitochondria, the organelles that play the central role in many cellular processes. The mitochondrial contact site and cristae organizing system (MICOS) together with the sorting and assembly machinery (SAM) forms the mitochondrial intermembrane space bridging complex (MIB), a large protein complex present in mammalian mitochondria that partakes in the formation and maintenance of cristae. We report here a new subunit of the mammalian MICOS/MIB complex, an armadillo repeat-containing protein 1 (ArmC1). ArmC1 localizes both to cytosol and mitochondria, where it associates with the outer mitochondrial membrane through its carboxy-terminus. ArmC1 interacts with other constituents of the MICOS/MIB complex and its amounts are reduced upon MICOS/MIB complex depletion. Mitochondria lacking ArmC1 do not show defects in cristae structure, respiration or protein content, but appear fragmented and with reduced motility. ArmC1 represents therefore a peripheral MICOS/MIB component that appears to play a role in mitochondrial distribution in the cell.

Highlights

  • Mitochondria are dynamic organelles performing various important cellular functions

  • armadillo repeatcontaining protein 1 (ArmC1) is a new mitochondrial intermembrane space bridging complex (MIB) component terminus of the protein (FLAG-ArmC1 and ArmC1-FLAG, respectively). Upon expression of these constructs in human cervical carcinoma (HeLa) cells, we observed that whereas ArmC1-FLAG did not appear to co-localize with mitochondria, but was evenly distributed in the cytosol, FLAG-ArmC1 was found largely associated with MitoTracker-stained mitochondria, a smaller amount of protein was detected in the cytosol, as well

  • The results were comparable, with ArmC1-green fluorescent protein (GFP) fluorescence distributed in the cytosol and GFP-ArmC1 signal mostly co-localizing with mitochondrial Tom20 signal, in addition to the weak cytosolic presence (Fig 1A)

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Summary

Introduction

Mitochondria are dynamic organelles performing various important cellular functions. ATP production, β-oxidation of fatty acids and synthesis of iron-sulfur clusters all take place within the mitochondria. Mitochondria have a central role in calcium homeostasis and programmed cell death [1]. Mitochondria are surrounded by two membranes, the outer (OMM) and the inner mitochondrial membrane (IMM), which enclose two additional compartments, the matrix, surrounded by the IMM, and the intermembrane space (IMS) between the OMM and the IMM. The OMM harbors the translocase of the outer membrane (TOM), which serves as an entry point for all proteins transported into mitochondria, and the sorting and assembly machinery.

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