Barbot, M. | Search bioRxiv

bioRxiv2025

Postural test to differentiate primary aldosteronism from low-renin hypertension

BackgroundThe diagnostic accuracy of screening and confirmatory tests to differentiate primary aldosteronism (PA) among patients with low-renin hypertension (HTN) is suboptimal. We aimed to assess the role of postural stimulation test (PST, previously used for PA subtyping) in differentiating PA from low-renin HTN. Patients and methodsClinical and endocrine data in clinostatic position (CP) and orthostatic position (OP) during PST were evaluated in 190 hypertensive patients: 80 PA and 110 low-renin HTN. Multivariate techniques were computed: Principal Component Analysis (PCA), Partial Least Square-Discriminant Analysis (PLS-DA) and k-means clustering. ResultsPST response differentiated our cohort: 96% of PA were detected in the 56/190 patients with always suppressed renin levels, 80% of patients with low-renin HTN were identified among 56/190 subjects with de-suppression of renin from CP to OP and 78/190 with always measurable renin. Increased potassium and measurable renin in OP were predictors of low-renin HTN. Cluster analysis distinguished PA from low-renin HTN: Cluster 2 included 104/110 low-renin HTN; Cluster 1 PA patients showed a higher frequency of suppressed renin levels at baseline and during PST (100% in CP and 95% in OP, respectively). Cluster 1 low-renin HTN patients had lower potassium and a higher frequency of suppressed renin levels at diagnosis and during PST, compared to Cluster 2. PLS-DA and PCA confirmed that renin in OP, renin response to PST and presence of hypokalemia were the most relevant parameters for distinguishing PA from low-renin HTN. ConclusionRenin response during PST can be used to differentiate PA from low-renin HTN.

physiology↗

bioRxiv2023

The Drosophila MIC10 orthologue has a propensity to polymerize into cristae-shaping filaments

Mitochondria are essential eukaryotic double-membrane organelles. The convoluted mitochondrial inner membrane forms highly organized invaginations, termed cristae, which are crucial for energy metabolism. Cristae formation requires MICOS, a conserved hetero-oligomeric inner membrane complex. The MICOS core subunit MIC10 is a small transmembrane protein that oligomerizes through highly conserved glycine-rich motifs to control cristae formation. Sequence alignments show that D. melanogaster exhibits three MIC10-like proteins with different tissue-specific expression patterns. Here, we show that the ubiquitously expressed Dmel_CG41128/MINOS1b/DmMIC10b is the major MIC10 orthologue in flies. Loss of DmMIC10b disturbs cristae architecture of mitochondria and reduces the life-span and fertility of flies. Moreover, using fluorescence nanoscopy and electron tomography, we demonstrate that despite its high similarity to the MIC10 proteins from yeast and humans, DmMIC10b exhibits the unique ability to polymerize into elongated filaments upon overexpression. DmMIC10b filaments form bundles which accumulate in the intermembrane space and alter the shape of mitochondrial cristae membranes. We show that the formation of the filaments relies on conserved glycine and cysteine residues and is suppressed by co-expression of other MICOS proteins. Thereby, our findings provide new insights into the regulation of MICOS in flies.

cell biology↗