Nijholt 2023 Sci Rep

Nijholt KT, Sánchez-Aguilera PI, Mahmoud B, Gerding A, Wolters JC, Wolters AHG, Giepmans BNG, Silljé HHW, de Boer RA, Bakker BM, Westenbrink BD (2023) A Kinase Interacting Protein 1 regulates mitochondrial protein levels in energy metabolism and promotes mitochondrial turnover after exercise. https://doi.org/10.1038/s41598-023-45961-z

» Sci Rep 13:18822. PMID: 37914850 Open Access

Nijholt Kirsten T, Sanchez-Aguilera Pablo I, Mahmoud Belend, Gerding Albert, Wolters Justina C, Wolters Anouk HG, Giepmans Ben NG, Sillje Herman HW, de Boer Rudolf A, Bakker Barbara M, Westenbrink B Daan (2023) Sci Rep

Abstract: A Kinase Interacting Protein 1 (AKIP1) is a signalling adaptor that promotes mitochondrial respiration and attenuates mitochondrial oxidative stress in cultured cardiomyocytes. We sought to determine whether AKIP1 influences mitochondrial function and the mitochondrial adaptation in response to exercise in vivo. We assessed mitochondrial respiratory capacity, as well as electron microscopy and mitochondrial targeted-proteomics in hearts from mice with cardiomyocyte-specific overexpression of AKIP1 (AKIP1-TG) and their wild type (WT) littermates. These parameters were also assessed after four weeks of voluntary wheel running. In contrast to our previous in vitro study, respiratory capacity measured as state 3 respiration on palmitoyl carnitine was significantly lower in AKIP1-TG compared to WT mice, whereas state 3 respiration on pyruvate remained unaltered. Similar findings were observed for maximal respiration, after addition of FCCP. Mitochondrial DNA damage and oxidative stress markers were not elevated in AKIP1-TG mice and gross mitochondrial morphology was similar. Mitochondrial targeted-proteomics did reveal reductions in mitochondrial proteins involved in energy metabolism. Exercise performance was comparable between genotypes, whereas exercise-induced cardiac hypertrophy was significantly increased in AKIP1-TG mice. After exercise, mitochondrial state 3 respiration on pyruvate substrates was significantly lower in AKIP1-TG compared with WT mice, while respiration on palmitoyl carnitine was not further decreased. This was associated with increased mitochondrial fission on electron microscopy, and the activation of pathways associated with mitochondrial fission and mitophagy. This study suggests that AKIP1 regulates the mitochondrial proteome involved in energy metabolism and promotes mitochondrial turnover after exercise. Future studies are required to unravel the mechanistic underpinnings and whether the mitochondrial changes are required for the AKIP1-induced physiological cardiac growth.

• Bioblast editor: Plangger M • O2k-Network Lab: NL Groningen Reijngoud RJ

Labels: MiParea: Respiration, Genetic knockout;overexpression, Exercise physiology;nutrition;life style 

Organism: Mouse  Tissue;cell: Heart  Preparation: Isolated mitochondria 

Coupling state: LEAK, OXPHOS, ET  Pathway: F, N  HRR: Oxygraph-2k 

2023-11