Mitochondrial Heterogeneity in Metabolic Diseases

Jennifer Ngo; Corey Osto; Frankie Villalobos; Orian S Shirihai

doi:10.3390/biology10090927

Mitochondrial Heterogeneity in Metabolic Diseases

Biology (Basel). 2021 Sep 17;10(9):927. doi: 10.3390/biology10090927.

Authors

Jennifer Ngo^{1

2

3}, Corey Osto^{1

3

4}, Frankie Villalobos^{1

5}, Orian S Shirihai^{1

3

4

6}

Affiliations

¹ Department of Medicine, Division of Endocrinology, David Geffen School of Medicine at UCLA, 650 Charles E. Young Drive East, Los Angeles, CA 90095, USA.
² Department of Chemistry and Biochemistry, University of California, 607 Charles E. Young Drive East, Los Angeles, CA 90095, USA.
³ Metabolism Theme, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
⁴ Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, 650 Charles E. Young Drive East, Los Angeles, CA 90095, USA.
⁵ Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA.
⁶ Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.

Abstract

Mitochondria have distinct architectural features and biochemical functions consistent with cell-specific bioenergetic needs. However, as imaging and isolation techniques advance, heterogeneity amongst mitochondria has been observed to occur within the same cell. Moreover, mitochondrial heterogeneity is associated with functional differences in metabolic signaling, fuel utilization, and triglyceride synthesis. These phenotypic associations suggest that mitochondrial subpopulations and heterogeneity influence the risk of metabolic diseases. This review examines the current literature regarding mitochondrial heterogeneity in the pancreatic beta-cell and renal proximal tubules as they exist in the pathological and physiological states; specifically, pathological states of glucolipotoxicity, progression of type 2 diabetes, and kidney diseases. Emphasis will be placed on the benefits of balancing mitochondrial heterogeneity and how the disruption of balancing heterogeneity leads to impaired tissue function and disease onset.

Keywords: calcium; heterogeneity; kidney diseases; lipotoxicity; membrane potential; mitochondria; morphology; subpopulations; type 2 diabetes.

Publication types

Review

Grants and funding

R25 GM055052/GM/NIGMS NIH HHS/United States