Structure and mechanism of mitochondrial electron transport chain

Abstract

Respiration is one of the most vital and basic features of living organisms. In mammals, respiration is accomplished by respiratory chain complexes located on the mitochondrial inner membrane. In the past century, scientists put tremendous efforts in understanding these complexes, but failed to solve the high resolution structure until recently. In 2016, three research groups reported the structure of respiratory chain supercomplex from different species, and fortunately the structure solved by our group has the highest resolution. In this review, we will compare the recently solved structures of respirasome, probe into the relationship between cristae shape and respiratory chain organization, and discuss the highly disputed issues afterwards. Besides, our group reported the first high resolution structure of respirasome and medium resolution structure of megacomplex from cultured human cells this year. Definitely, these supercomplex structures will provide precious information for conquering the mitochondrial malfunction diseases.

Keywords: Assembly of respirasome; Cristae organization; Electron transfer pathway; Structure of respirasome; Substrate channeling.

Fig. 1

Overall structures and conformational changes of respirasome from porcine, ovine and bovine (A). High resolution structure of respirasome from porcine heart. Front and back view of cartoon models are shown. Each subunit is shown in different colors. These structures are originated from data in PDB: 5GUP. (B) Conformational change of CI and CIII. Two conformations of CI and CIII are shown in marine and cyan respectively. (C) Conformational change of CIV. CIV is shown in yellow, while CI and CIII are shown in blue in respirasome. Relative distance between CIII and CIV are variable through different species and conformations. Model of respirasome from porcine, bovine, ovine (tight), ovine (loose) are originated from PDB 5GUP, 5LUF, 5J4Z and 5J7Y respectively , , , .

Fig. 2

The relationship between cristae shape and respirasome. Simple cartoon model of cristae and OXPHOS proteins are shown. Respirasome and individual complexes are located on the planar cristae surface. ATP synthase dimer sits at the edge of cristae. The of root of cristae is lashed by OPA1 oligomers. Abbreviation: IMS: Intermembrane space. Traces of proton are shown by arrows.

Fig. 3

Linear and circular model of megacomplex Linear model (A) and circular model (B) of megacomplex organization are shown. CI, CIII and CIV are in green, mega and yellow respectively , .

Fig. 4

Different electron transfer mechanisms. Two mechanisms proposed by different groups are presented and depicted in the paragraph. Complex I, III, IV and cyt.c are shown in cyan, green, brown and purple respectively. Electron transfer pathway is indicated by arrows. Abbreviation: IMS: Intermembrane space.