Protein composition of the muscle mitochondrial reticulum during postnatal development

Abstract

Key pointsr Muscle mitochondrial networks changed from a longitudinal, fibre parallel orientation to a perpendicular configuration during postnatal development.r Mitochondrial dynamics, mitophagy and calcium uptake proteins were abundant during early postnatal development.r Mitochondrial biogenesis and oxidative phosphorylation proteins were upregulated throughout muscle development.r Postnatal muscle mitochondrial network formation is accompanied by a change in protein expression profile from mitochondria designed for co-ordinated cellular assembly to mitochondria highly specialized for cellular energy metabolism.Abstract Striated muscle mitochondria form connected networks capable of rapid cellular energy distribution. However, the mitochondrial reticulum is not formed at birth and the mechanisms driving network development remain unclear. In the present study, we aimed to establish the network formation timecourse and protein expression profile during postnatal development of the murine muscle mitochondrial reticulum. Two-photon microscopy was used to observe mitochondrial network orientation in tibialis anterior (TA) muscles of live mice at postnatal days (P) 1, 7, 14, 21 and 42, respectively. All muscle fibres maintained a longitudinal, fibre parallel mitochondrial network orientation early in development (P1-7). Mixed networks were most common at P14 but, by P21, almost all fibres had developed the perpendicular mitochondrial orientation observed in mature, glycolytic fibres. Tandem mass tag proteomics were then applied to examine changes in 6869 protein abundances in developing TA muscles. Mitochondrial proteins increased by 32% from P1 to P42. In addition, both nuclear-and mitochondrial-DNA encoded oxidative phosphorylation (OxPhos) components were increased during development, whereas OxPhos assembly factors decreased. Although mitochondrial dynamics and mitophagy were induced at P1-7, mitochondrial biogenesis was enhanced after P14. Moreover, calcium signalling Y. Kim and others J Physiol 597.10 proteins and the mitochondrial calcium uniporter had the highest expression early in postnatal development. In conclusion, mitochondrial networks transform from a fibre parallel to perpendicular orientation during the second and third weeks after birth in murine glycolytic skeletal muscle. This structural transition is accompanied by a change in protein expression profile from mitochondria designed for co-ordinated cellular assembly to mitochondria highly specialized for cellular energy metabolism.

Cell energy metabolism: An update

“…A number of studies have evidenced a modulation of cellular oxidative phosphorylation activity either in yeast during diauxic shift [48][49][50][51][52][53] or in mammals in different tissues, during development and cell differentiation, and in various physio-pathological situations [54][55][56][57][58][59][60][61][62][63]. However, in order to decipher the origin and molecular mechanisms involved in this process, a robust evaluation and definition of mitochondrial content and activity in cells is required.…”

“…However, it has been shown that the mitochondrial compartment might not vary as a whole but that there could be specific enrichment of some components and metabolic pathways [48,59,62,77,78] hinting that the volume of the organelle might be useful but not sufficient to depict the amount of material depending on the question addressed. Another approach would be to quantify mitochondrial proteins or lipids such as cardiolipin that only belong to the mitochondrial membrane.…”

“…It might be insightful to use protein markers from different mitochondrial compartments and processes, for instance components of the oxidative phosphorylation and metabolic pathways, but also of house-keeping functions such as protein import, chaperones, or mtDNA maintenance and expression. Proteomics approaches may be necessary to appreciate the overall differential regulation of mitochondrial proteins [62]. The amount of mitochondrial DNA has often been shown to correlate well with the amount of mitochondria and mitochondrial proteins [55-57,60,66,82].…”

Mitochondrial light switches: optogenetic approaches to control metabolism

“…For example, substrate and oxygen availability [10,14] or energetic demand from exercise [15–17] can alter the PMF. Metabolic conditions can vary between tissues, and accordingly, there are tissue differences in mitochondrial PMF [18,19]. The PMF can also be differentially regulated within individual mitochondria, with separate matrix cristae compartments able to experience different driving forces [20].…”

Morphing mitochondria: understanding the development of the mitochondrial reticulum in skeletal muscle

“…In this issue of The Journal of Physiology , Kim et al . () provide an unprecedented and detailed analysis of the postnatal developmental time course of the mitochondrial reticulum and the corresponding changes in protein composition in skeletal muscle of mice.…”