Table 2.

Endogenous MDP response to metabolic stressors in vivo

Reference(s)	Metabolic Stress	MDP	Tissue	Effect
Aging
Muzumdar et al. (44), Bachar et al. (1), D’Souza et al. (8)	Aging (human)	Humanin, MOTS-c	Blood	↓
Conte et al. (7)	Aging (human)	Humanin	Blood	↑
D’Souza et al. (8)	Aging (human)	MOTS-c	Muscle	↑
Muzumdar et al. (44), Cobb et al. (6), Lee et al. (31)	Aging (rodent)	Humanin, MOTS-c, SHLP2	Blood, muscle, hypothalamus	↓
Exercise
Woodhead et al. (54)	AEx (human)	Humanin	Muscle, blood	↑,↑
Woodhead et al. (54)	TRx (human)		Muscle, blood	↔, ↓
Woodhead et al. (54)	AEx, TRx (human)	SHLP2	Blood	↔
Woodhead et al. (54)	AEx, TRx (human)	SHLP6	Blood	↑, ↓
Reynolds et al. (50)	AEx (human)	MOTS-c	Muscle, blood	↑,↑
Gidlund et al. (11)	TRx (human)	Humanin	Muscle, blood	↑↔,↔
Ramanjenaya et al. (49)	TRx (human)	MOTS-c	Blood	↔
Cardiovascular
Widmer et al. (53), Zhloba et al. (60), Qin et al. (47)	Heart disease (human)	Humanin	Blood	↓
Mangkhang et al. (37)	Mitral valve disease (canine)	Humanin	Blood	↓
Metabolic disorders
Ramanjaneya et al. (48)	Type 2 diabetes (human)	Humanin, MOTS-c	Blood	↓
Cataldo et al. (4)	IR (human)	MOTS-c	Blood	↑
Cataldo et al. (4)	Obesity (human)	MOTS-c	Blood	↔
Du et al. (9)	Obesity (human)	MOTS-c	Blood	↓
Liu et al. (33)	Kidney disease (human)	MOTS-c, Humanin	Muscle, blood Muscle, blood Muscle	↓ ↓,↑ ↑#
Other
Lu et al. (35)	Cold exposure (rodent)	MOTS-c	Blood	↓
Ramanjaneya et al. (49)	Intralipid infusion (human)	MOTS-c	Blood	↑
Kariya et al. (19), Kin et al. (25)	mtDNA-related diseases (human)	Humanin	Muscle	↑

AEx, acute exercise bout; blood, serum or plasma; IR, insulin resistance; MDP, mitochondrial-derived peptide; TRx, exercise training. ↑, increase; ↓, decrease; ↔, no change;

^#Relative to mtDNA.