Unraveling the Phosphoproteome Dynamics in Mammal Mitochondria from a Network Perspective

• Type: Another Publication in an International Scientific Journal
• Date: 2013

Authors

padrao, ai (Author) Other; vitorino, r (Author) Other; duarte, ja (Author) FADEUP; ferreira, r (Author) Other; amado, f (Author) Other

Journal

Title: Journal of Proteome Research

Vol. 12

Pages: 4257-4267

ISSN: 1535-3893

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 14 Citations

Scopus - 15 Citations

Other information

Authenticus ID: P-008-EXB

DOI: 10.1021/pr4003917

Abstract (EN): With mitochondrion garnering more attention for its inextricable involvement in pathophysiological conditions, it seems imperative to understand the means by which the molecular pathways harbored in this organelle are regulated. Protein phosphorylation has been considered a central event in cellular signaling and, more recently, in the modulation of mitochondrial activity. Efforts have been made to understand the molecular mechanisms by which protein phosphorylation regulates mitochondrial signaling. With the advances in mass-spectrometry-based proteomics, there is a substantial hope and expectation in the increased knowledge of protein phosphorylation profile and its mode of regulation. On the basis of phosphorylation profiles, attempts have been made to disclose the kinases involved and how they control the molecular processes in mitochondria and, consequently, the cellular outcomes. Still, few studies have focused on mitochondrial phosphoproteome profiling, particularly in diseases. The present study reviews current data on protein phosphorylation profiling in mitochondria, the potential kinases involved and how pathophysiological conditions modulate the mitochondrial phosphoproteome. To integrate data from distinct research papers, we performed network analysis, with bioinformatic tools like Cytoscape, String, and PANTHER taking into consideration variables such as tissue specificity, biological processes, molecular functions, and pathophysiological conditions. For instance, data retrieved from these analyses evidence some homology in the mitochondrial phosphoproteome among liver and heart, with proteins from transport and oxidative phosphorylation clusters particularly susceptible to phosphorylation. A distinct profile was noticed for adipocytes, with proteins form metabolic processes, namely, triglycerides metabolism, as the main targets of phosphorylation. Regarding disease conditions, more phosphorylated proteins were observed in diabetics with some distinct phosphoproteins identified in type 2 prediabetic states and early type 2 diabetes mellitus. Heart-failure-related phosphorylated proteins are in much lower amount and are mainly involved in transport and metabolism. Nevertheless, technical considerations related to mitochondria isolation and protein separation should be considered in data comparison among different proteomic studies. Data from the present review will certainly open new perspectives of protein phosphorylation in mitochondria and will help to envisage future studies targeting the underlying regulatory mechanisms.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11