Two Types of Contact Between Lipid Droplets and Mitochondria

Abstract

Lipid droplets (LDs) and mitochondria are essential organelles involved in cellular lipid metabolism and energy homeostasis. Accumulated studies have revealed that the physical contact between these two organelles is important for their functions. Current understanding of the contact between cellular organelles is highly dynamic, fitting a “kiss-and-run” model. The same pattern of contact between LDs and mitochondria has been reported and several proteins are found to mediate this contact, such as perilipin1 (PLIN1) and PLIN5. Another format of the contact has also been found and termed anchoring. LD-anchored mitochondria (LDAM) are identified in oxidative tissues including brown adipose tissue (BAT), skeletal muscle, and heart muscle, and this anchoring between these two organelles is conserved from mouse to monkey. Moreover, this anchoring is generated during the brown/beige adipocyte differentiation. In this review, we will summarize previous studies on the interaction between LDs and mitochondria, categorize the types of the contacts into dynamic and stable/anchored, present their similarities and differences, discuss their potential distinct molecular mechanism, and finally propose a working hypothesis that may explain why and how cells use two patterns of contact between LDs and mitochondria.

A comprehensive approach to artifact-free sample preparation and the assessment of mitochondrial morphology in tissue and cultured cells

“…Insulin increases mitochondrial fusion in cultured cardiomyocytes and skeletal muscle cells 1 . Insulin stimulation results in larger, fused mitochondria with increased integrated cristae density 1 .…”

“…Insulin increases mitochondrial fusion in cultured cardiomyocytes and skeletal muscle cells 1 . Insulin stimulation results in larger, fused mitochondria with increased integrated cristae density 1 . Thus, using an insulin stimulation model permitted the validation of specimen preparation conditions under experimental conditions that increased mitochondrial size and cristae density.…”

“…Thus, using an insulin stimulation model permitted the validation of specimen preparation conditions under experimental conditions that increased mitochondrial size and cristae density. Before fixation, cells were treated with 2 hours of insulin stimulation 1 . The cultures were then prepared using a variety of harvesting and fixation methods to determine the optimal procedures for imaging.…”

“…Importantly, the balance between health and disease rests, in part, on environmental, genetic, and biochemical factors that influence mitochondrial function. Dynamic transitions in mitochondrial characteristics can reflect normal and disease-related changes in mitochondrial size and shape, changes in network structures, and altered interactions with other organelles 1–11 1–11 . Mitochondrial number and shape are determined, in part, by fusion and fission cycles 1–6 1–6 , which are coordinated by the fusion genes, optic atrophy 1 (OPA-1) and mitofusin 1 and 2 (MFN-1 and MFN2, respectively), the fission protein dynamin-related protein 1 (DRP-1) and its receptors, mitochondrial fission 1 (FIS1), mitochondrial fission factor (MFF), and mitochondrial dynamics protein MiD49 and MiD51 1–6 1–6 .…”

“…The objectives of this study were to 1) develop an optimized approach for specimen handling and fixation to preserve mitochondrial morphology, 2) optimize methodology for quantifying organelle characteristics using transmission electron microscopy (TEM) micrographs, and 3) validate the reproducibility of these methods for describing morphological changes in subcellular organelles. We focused on methods for quantifying indices of mitochondrial morphology 1–6 , such as hyperbranching, mitochondrial volume, cristae morphology 7–11 , as well as the length and percentage coverage of MERCs 12–16 . To further validate our approach, we deleted genes encoding known mitochondrial dynamics proteins, such as OPA-1, MFN-2, and DRP-1, to evaluate which methodology was the most reproducible and representative of mitochondrial changes.…”