bims-mecosi 2026-01-25 papers

Issue of 2026–01–25
two papers selected by
Verena Kohler, Umeå University

Mov Disord. 2026 Jan 19.

VPS13A Deficiency Leads to Impaired Lipid Distribution and Alteration of Mitochondrial Calcium Homeostasis in Fibroblasts of VPS13A Disease Patients.

Dajana Grossmann, Adrian Spranger, Emily Fischer, Johanna W Schubarth, Jenny Leopold, Hannes Glaß, Sebastian Klicker, My Uyen Dang Thi, Anna Elisabeth Bartalis, Andreas Hermann, Kevin Peikert.

BACKGROUND: Membrane contact sites are crucial for the exchange of ions or lipids and thus are critical for the function and maintenance of organelles. VPS13A is a membrane-residing, bridge-like protein connecting two membranes to enable bulk lipid transfer. Loss-of-function mutations in the VPS13A gene cause VPS13A disease. Previous studies showed alterations of lipid transfer and impaired calcium homeostasis.
OBJECTIVE: Although membrane contact sites are becoming increasingly important in neurodegenerative disease research, their contribution to cellular homeostasis is still unclear. We attempted to investigate the consequences of loss of VPS13A function on membrane contact sites and related mechanisms in the context of VPS13A disease.
METHODS: VPS13A-deficient patient-derived fibroblasts were compared with fibroblasts from healthy donors. Specific dyes, labeled fatty acids, and a specific marker for mitochondrial-endoplasmic reticulum contact sites were used to investigate lipid transfer and distribution in involved organelles. Mitochondrial calcium handling was investigated using the calcium indicator Rhod-2, AM. Images were obtained by super-resolution microscopy using Airyscan2 technology.
RESULTS: We observed a general disturbance of membrane contact sites in VPS13A disease, accompanied by a reduction in lipid droplet formation, diminished lipid transfer into mitochondria, and unusual mitochondrial calcium uptake behavior in VPS13A disease fibroblasts.
CONCLUSIONS: Loss of VPS13A causes alterations beyond an impairment of lipid shuttling, which includes a dysregulation of membrane contact sites as well as impaired mitochondrial calcium handling. Accordingly, our findings contribute significantly to the understanding of mechanisms directly or indirectly linked to the function of VPS13A. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: Bridge‐like lipid‐transport proteins (BLTPs); MERCS; VPS13A; calcium; lipids; mitochondria

DOI: https://doi.org/10.1002/mds.70177

Aging Adv. 2025 Dec 18.

Roles of DRP1 and the fission protein interactome as regulators of cellular stability and sarcopenia in skeletal muscle aging.

C Nivedya, Prasanna Venkhatesh, Benjamin I Rodriguez, Han Le, Jeremiah Afolabi, Andrea Marshall, Kit Neikirk, Sepiso K Masenga, Muhammad Aftab, Leo Jake Kazma, Prasanna Katti, Antentor Hinton.

Mitochondrial function is crucial in regulating cellular activity and determining cell fate. The replication and transcription of mitochondrial DNA are essential for maintaining mitochondrial integrity. These processes are governed by mitochondrial fission and fusion, which play a vital role in energy distribution, quality control, and metabolic regulation. Mitochondrial fission relies on the coordinated actions of mitochondria-endoplasmic reticulum contact sites, actin filaments, and dynamin-related protein 1, which collectively mediate mitochondrial constriction and fission. This interplay is fundamental to mitochondrial homeostasis and, critically, to the functionality of skeletal muscle. In this review, we explore the complex interactions among dynamin-related protein 1, mitochondria-endoplasmic reticulum contact sites, and actin and their significance for skeletal muscle function. Additionally, we discuss potential strategies to preserve these interactions, supporting optimal muscle performance in skeletal muscle aging. This review provides key insights and outlines future research directions to advance our understanding of this essential yet widely studied relationship.

Keywords: dynamin-related protein 1 (DRP1); exercise interventions; fission and fusion; mitochondria quality control; mitochondrial dynamics; mitochondria–endoplasmic reticulum contact sites (MERCs); mitophagy; posttranslational modifications; sarcopenia; skeletal muscle aging

DOI: https://doi.org/10.4103/agingadv.agingadv-d-25-00013