Mitochondrial protein import: from proteomics to functional mechanisms

Abstract

Mitochondria contain approximately 1,000 different proteins, most of which are imported from the cytosol. Two import pathways that direct proteins into the mitochondrial inner membrane and matrix have been known for many years. The identification of numerous new transport components in recent proteomic studies has led to novel mechanistic insight into these pathways and the discovery of new import pathways into the outer membrane and intermembrane space. Protein translocases do not function as independent units but are integrated into dynamic networks and are connected to machineries that function in bioenergetics, mitochondrial morphology and coupling to the endoplasmic reticulum.

Improved tolerance to salt and water stress in Drosophila melanogaster cells conferred by late embryogenesis abundant protein

“…All mitochondrial matrix proteins are encoded by nuclear genes and are transported across the outer and inner mitochondrial membrane after being synthesized by cytoplasmic ribosomes ( (Attardi and Schatz, 1988;Chacinska et al, 2009;Lemire et al, 1989;Schmidt et al, 2010). Similar to other proteins destined for the matrix, AfLEA1.3 contains a positively charged N-terminal pre-sequence; the projected cleavage site is after amino-acid position 36 but has not been experimentally confirmed.…”

Tom70 serves as a molecular switch to determine pathological cardiac hypertrophy

“…The precise targeting of mitochondrial precursor proteins requires the recognition of mitochondrial targeting signals. Tom20 and Tom70 recognize mitochondrial-targeting sequences on the precursor proteins and transfer these preproteins to Tom22 and the central channel [7,8]. Accumulating evidence indicates that the assembly of the Tom complex exhibits obvious plasticity in response to a variety of stressors, including enhanced contractile activity of skeletal muscle [9] and elevated levels of thyroid hormones and cytosolic kinases [10,11].…”

“…The vast majority of mitochondrial proteins are encoded by nuclear DNA, synthesized as precursor proteins in the cytosol, and imported into the mitochondria; only ~1% of mitochondrial proteins are encoded by mitochondrial DNA. The dynamic import of these precursor proteins into mitochondria is critically required for the maintenance of mitochondrial functions ranging from cell signaling to the regulation of cell fate beyond intrinsic energy generation [7].…”

A component of the mitochondrial outer membrane proteome of T. brucei probably contains covalent bound fatty acids

“…In general, protein import across -or insertion into -the MOM is mediated by a protein complex termed TOM (translocase of the MOM; for recent reviews see e.g. (Becker et al, 2009;Schmidt et al, 2010). Trypanosomes have an unusual TOM complex, the central component of which is ATOM40 (ATOM = archaic translocase of the MOM, see Pusnik et al, 2011;Harsman et al, 2012;Mani et al, 2015).…”